Publications by authors named "Guiyuan Li"

335 Publications

BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer.

Front Cell Dev Biol 2021 24;9:659392. Epub 2021 May 24.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7) and BRD7 (BRD7) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7 mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin-proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth and . In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin-proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.
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http://dx.doi.org/10.3389/fcell.2021.659392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181413PMC
May 2021

Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ.

J Exp Clin Cancer Res 2021 Jun 9;40(1):190. Epub 2021 Jun 9.

Hunan Provincial Cancer Hospital and Cancer Hospital Affiliated to Xiangya Medical School, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.

Background: Pyroptosis is a lytic cell death form executed by gasdermins family proteins. Induction of tumor pyroptosis promotes anti-tumor immunity and is a potential cancer treatment strategy. Triptolide (TPL) is a natural product isolated from the traditional Chinese herb which possesses potent anti-tumor activity in human cancers. However, its role in pyroptosis remains to be elucidated.

Methods: Cell survival was measured by colony formation assay. Cell apoptosis was determined by Annexin V assay. Pyroptosis was evaluated by morphological features and release of interleukin 1β and lactate dehydrogenase A (LDHA). Immunofluorescence staining was employed to measure subcellular localization of proteins. Tumorigenicity was assessed by a xenograft tumor model. Expression levels of mRNAs or proteins were determined by qPCR or western blot assay, respectively.

Results: Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis. Silencing GSDME attenuates the cytotoxicity of TPL against cancer cells. TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3. Silencing HK-II sensitizes cancer cells to TPL induced pyroptosis, whereas enforced expression of HK-II prevents TPL induced pyroptosis. Mechanistically, HK-II prevents mitochondrial translocation of BAD, BAX proteins and activation of caspase 3, thus attenuating cleavage of GSDME and pyroptosis upon TPL treatment. Furthermore, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME. Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model.

Conclusions: This study not only provides a new paradigm of TPL in cancer therapy, but also highlights a crucial role of mitochondrial HK-II in linking glucose metabolism with pyroptosis.
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http://dx.doi.org/10.1186/s13046-021-01995-7DOI Listing
June 2021

Lung microbiome alterations in NSCLC patients.

Sci Rep 2021 Jun 3;11(1):11736. Epub 2021 Jun 3.

Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Lung is colonized by a diverse array of microbes and the lung microbiota is profoundly involved in the development of respiratory diseases. There is little knowledge about the role of lung microbiota dysbiosis in lung cancer. In this study, we performed metagenomic sequencing on bronchoalveolar lavage (BAL) from two different sampling methods in non-small cell lung cancer (NSCLC) patients and non-cancer controls. We found the obvious variation between bronchoscopy samples and lobectomy samples. Oral taxa can be found in both bronchoscopy and lobectomy samples and higher abundance of oral taxa can be found in bronchoscopy samples. Although the NSCLC patients had similar microbial communities with non-cancer controls, rare species such as Lactobacillus rossiae, Bacteroides pyogenes, Paenibacillus odorifer, Pseudomonas entomophila, Magnetospirillum gryphiswaldense, fungus Chaetomium globosum et al. showed obvious difference between NSCLC patients and non-cancer controls. Age-, gender-, and smoking-specific species and EGFR expression-related species in NSCLC patients were detected. There results implicated that different lung segments have differential lung microbiome composition. The oral taxa are found in the lobectomy samples suggesting that oral microbiota are the true members of lung microbiota, rather than contamination during bronchoscopy. Lung cancer does not obviously alter the global microbial composition, while rare species are altered more than common species. Certain microbes may be associated with lung cancer progression.
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http://dx.doi.org/10.1038/s41598-021-91195-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175694PMC
June 2021

AFAP1-AS1: a rising star among oncogenic long non-coding RNAs.

Sci China Life Sci 2021 May 13. Epub 2021 May 13.

NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China.

Long non-coding RNAs (lncRNAs) have become a hotspot in biomedical research. This interest reflects their extensive involvement in the regulation of the expression of other genes, and their influence on the occurrence and development of a variety of human diseases. Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1) is a recently discovered oncogenic lncRNA. It is highly expressed in a variety of solid tumors, and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs, or by the direct binding to other proteins. Ultimately, AFAP1-AS1 promotes proliferation, chemotherapy resistance, and resistance to apoptosis, maintains stemness, and enhances invasion and migration of tumor cells. This paper summarizes the research concerning AFAP1-AS1 in malignant tumors, including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors. We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research. AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.
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http://dx.doi.org/10.1007/s11427-020-1874-6DOI Listing
May 2021

Research Progress of circRNAs in Head and Neck Cancers.

Front Oncol 2021 29;11:616202. Epub 2021 Apr 29.

Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Because of their characteristics of a closed loop structure, disease- and tissue-specificity, and high conservation and stability, circRNAs have the potential to be biomarkers for disease diagnosis. Head and neck cancers are one of the most common malignant tumors with high incidence rates globally. Affected patients are often diagnosed at the advanced stage with poor prognosis, owing to the concealment of anatomic sites. The characteristics, functions, and specific mechanisms of circRNAs in head and neck cancers are increasingly being discovered, and they have important clinical significance for the early diagnosis, treatment, and prognosis evaluation of patients with cancer. In this study, the generation, characteristics, and functions of circRNAs, along with their regulatory mechanisms in head and neck cancers have been summarized. We report that circRNAs interact with molecules such as transcription and growth factors to influence specific pathways involved in tumorigenesis. We conclude that circRNAs have an important role to play in the proliferation, invasion, metastasis, energy and substance metabolism, and treatment resistance in cancers.
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http://dx.doi.org/10.3389/fonc.2021.616202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117014PMC
April 2021

RNA-binding protein YBX1 promotes cell proliferation and invasiveness of nasopharyngeal carcinoma cells binding to AURKA mRNA.

J Cancer 2021 7;12(11):3315-3324. Epub 2021 Apr 7.

The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

RNA-binding proteins (RBPs) play essential roles in post-transcriptional control of gene expression. Dysregulation of RBPs is intensively implicated in development and progression of human diseases, including cancers. However, the roles of RBPs in nasopharyngeal carcinoma (NPC), which is a distinct subtype of head and neck cancer, remain elusive. NPC-related RBPs were explored by analyzing GEO database and high-throughput proteomic data obtained from crosslinking immunoprecipitation. The expression levels of Y box binding protein 1 (YBX1) protein in NPC samples were measured by immunohistochemistry (IHC) staining. The association of YBX1 protein levels with prognosis of NPC patients was analyzed by Kaplan-Meier Plotter. The expression levels of YBX1 in NPC cells were inhibited by RNA interference. Cell growth was measured by CCK-8 assay. Cell mobility and invasiveness were measured by transwell assays. Tumorigenicity was measured by using a xenograft tumor assay. The expression levels of mRNAs or proteins were determined by qPCR or western blot assays, respectively. The mRNAs binding to YBX1 were determined by RNA immunoprecipitation (RIP) and qPCR. The effect of YBX1 on mRNA translation was measured by luciferase reporter assay. In the present study, we demonstrated a differentially expressed RBPs profile between NPC and its normal counterpart. Among these aberrantly expressed RBPs, YBX1 was overexpressed in NPC. We found that YBX1 is mainly localized in the cytoplasm of NPC cells. Loss of YBX1 led to reduced cell proliferation, migration and invasiveness , and reduced tumorigenicity . Overexpression of YBX1 associates with high expression of cell cycle G2/M checkpoint modulators. In addition, YBX1 promotes AURKA protein expression by directly binding to its mRNA. Loss of YBX1 leads to reduction of AURKA protein level. Forced expression of AURKA rescues cell proliferation and invasiveness in YBX1-silenced NPC cell. The current study indicated that YBX1 promotes NPC cell proliferation and invasiveness through enhancing protein synthesis of AURKA.
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http://dx.doi.org/10.7150/jca.56262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100805PMC
April 2021

What are the applications of single-cell RNA sequencing in cancer research: a systematic review.

J Exp Clin Cancer Res 2021 May 11;40(1):163. Epub 2021 May 11.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Single-cell RNA sequencing (scRNA-seq) is a tool for studying gene expression at the single-cell level that has been widely used due to its unprecedented high resolution. In the present review, we outline the preparation process and sequencing platforms for the scRNA-seq analysis of solid tumor specimens and discuss the main steps and methods used during data analysis, including quality control, batch-effect correction, normalization, cell cycle phase assignment, clustering, cell trajectory and pseudo-time reconstruction, differential expression analysis and gene set enrichment analysis, as well as gene regulatory network inference. Traditional bulk RNA sequencing does not address the heterogeneity within and between tumors, and since the development of the first scRNA-seq technique, this approach has been widely used in cancer research to better understand cancer cell biology and pathogenetic mechanisms. ScRNA-seq has been of great significance for the development of targeted therapy and immunotherapy. In the second part of this review, we focus on the application of scRNA-seq in solid tumors, and summarize the findings and achievements in tumor research afforded by its use. ScRNA-seq holds promise for improving our understanding of the molecular characteristics of cancer, and potentially contributing to improved diagnosis, prognosis, and therapeutics.
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http://dx.doi.org/10.1186/s13046-021-01955-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111731PMC
May 2021

The long noncoding RNA AATBC promotes breast cancer migration and invasion by interacting with YBX1 and activating the YAP1/Hippo signaling pathway.

Cancer Lett 2021 Aug 2;512:60-72. Epub 2021 May 2.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Long noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown. In this study, the lncRNA apoptosis-associated transcript in bladder cancer (AATBC) was found to be significantly highly expressed in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer metastasis. Further studies revealed that AATBC activated the YAP1/Hippo signaling pathway through the AATBC-YBX1-MST1 axis. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of "AATBC-YAP1" may bring a new dawn to the treatment of breast cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.04.025DOI Listing
August 2021

Pyroptosis: a new paradigm of cell death for fighting against cancer.

J Exp Clin Cancer Res 2021 May 3;40(1):153. Epub 2021 May 3.

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.

Background: Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer.

Main Body: Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies.

Conclusion: In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.
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http://dx.doi.org/10.1186/s13046-021-01959-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091792PMC
May 2021

EpsteinBarr virusencoded microRNAs involve in tumorigenesis and development.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Mar;46(3):300-308

Institute of Cancer Research, Central South University, Changsha 410078, China.

Epstein-Barr virus (EBV), a definite tumorigenic virus, is closely related to the development of nasopharyngeal cancer, gastric cancer, lymphoma and other tumors. EBV encodes a total of 44 mature microRNAs, which can regulate the expression of virus and host genes. EBV-encoded microRNAs and their regulated target molecules participate in the biological functions of tumor apoptosis, proliferation, invasion, and metastasis during tumorigenesis and development, and play an important role in the development of tumor.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.190744DOI Listing
March 2021

N6-methyladenosine-dependent signalling in cancer progression and insights into cancer therapies.

J Exp Clin Cancer Res 2021 Apr 29;40(1):146. Epub 2021 Apr 29.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

The N6-methyladenosine (m6A) modification is a dynamic and reversible epigenetic modification, which is co-transcriptionally deposited by a methyltransferase complex, removed by a demethylase, and recognized by reader proteins. Mechanistically, m6A modification regulates the expression levels of mRNA and nocoding RNA by modulating the fate of modified RNA molecules, such as RNA splicing, nuclear transport, translation, and stability. Several studies have shown that m6A modification is dysregulated in the progression of multiple diseases, especially human tumors. We emphasized that the dysregulation of m6A modification affects different signal transduction pathways and involves in the biological processes underlying tumor cell proliferation, apoptosis, invasion and migration, and metabolic reprogramming, and discuss the effects on different cancer treatment.
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http://dx.doi.org/10.1186/s13046-021-01952-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082653PMC
April 2021

The influence of circular RNAs on autophagy and disease progression.

Autophagy 2021 Apr 27:1-14. Epub 2021 Apr 27.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Circular RNAs (circRNAs) are non-coding RNAs that have attracted considerable attention in recent years. Owing to their distinct circular structure, circRNAs are stable in cells. Autophagy is a catabolic process that helps in the degradation and recycling of harmful or inessential biological macromolecules in cells and enables cells to adapt to stress and changes in the internal and external environments. Evidence has shown that circRNAs influence the course of a disease by regulating autophagy, which indicates that autophagy is involved in the onset and development of various diseases and can affect drug resistance (for example, it affects cisplatin resistance in tumors). In this review, we summarized the role of circRNAs in autophagy and their influence on disease onset and progression as well as drug resistance. The review will expand our understanding of tumors as well as cardiovascular and neurological diseases and also suggest novel therapeutic strategies.: : autophagy-related circRNA; ADSCs: adipogenic mesenchymal stem cells; AMPK: AMP-activated protein kinase; ATG: autophagy related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; ceRNA: competing endogenous RNA; circRNA: circular RNA; CMA: chaperone-mediated autophagy; EPCs: endothelial progenitor cells; LE/MVBs: late endosomes/multivesicular bodies; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NSCLC: non-small cell lung cancer; PDLSCs: periodontal ligament stem cells; PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate 1,2-dipalmitoyl; PTEN: phosphatase and tensin homolog; RBPs: RNA-binding proteins; SiO: silicon dioxide; TFEB: transcription factor EB; ULK: unc-51 like autophagy activating kinase 1.
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http://dx.doi.org/10.1080/15548627.2021.1917131DOI Listing
April 2021

Single-cell RNA sequencing in cancer research.

J Exp Clin Cancer Res 2021 Mar 1;40(1):81. Epub 2021 Mar 1.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, China.

Single-cell RNA sequencing (scRNA-seq), a technology that analyzes transcriptomes of complex tissues at single-cell levels, can identify differential gene expression and epigenetic factors caused by mutations in unicellular genomes, as well as new cell-specific markers and cell types. scRNA-seq plays an important role in various aspects of tumor research. It reveals the heterogeneity of tumor cells and monitors the progress of tumor development, thereby preventing further cellular deterioration. Furthermore, the transcriptome analysis of immune cells in tumor tissue can be used to classify immune cells, their immune escape mechanisms and drug resistance mechanisms, and to develop effective clinical targeted therapies combined with immunotherapy. Moreover, this method enables the study of intercellular communication and the interaction of tumor cells and non-malignant cells to reveal their role in carcinogenesis. scRNA-seq provides new technical means for further development of tumor research and is expected to make significant breakthroughs in this field. This review focuses on the principles of scRNA-seq, with an emphasis on the application of scRNA-seq in tumor heterogeneity, pathogenesis, and treatment.
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http://dx.doi.org/10.1186/s13046-021-01874-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919320PMC
March 2021

EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling.

Br J Cancer 2021 Mar 21;124(7):1301-1311. Epub 2021 Jan 21.

First Department of thoracic surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Background: Eukaryotic protein translation elongation factor 1α2 (EEF1A2) is an oncogene that promotes the progression of breast and pancreatic cancer. In this study, we aimed to elucidate the oncogenic function of EEF1A2 in the metastasis of lung adenocarcinoma (LUAD).

Methods: Immunohistochemistry and western blot were used to study EEF1A2 expression levels in LUAD tissues and cells, respectively. The role of EEF1A2 in LUAD progression were investigated in vitro and in vivo. We identified potential EEF1A2-binding proteins by liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. Protein-protein interactions were determined by immunofluorescence and co-immunoprecipitation (Co-IP).

Results: In this study, we report that EEF1A2 mediates the epithelial-mesenchymal transformation (EMT), to promote the metastasis of LUAD cells in vitro and in vivo. Moreover, EEF1A2 interacts with HSP90AB1 to increase TGFβ Receptor (TβR)-I, and TβRII expression, followed by enhanced SMAD3 and pSMAD3 expression and nuclear localisation, which promotes the EMT of LUAD cells. Overexpression of EEF1A2 in cancer tissues is associated with poor prognosis and short survival of patients with LUAD.

Conclusions: These findings underscore the molecular functions of EEF1A2 in LUAD metastasis and indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD.
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http://dx.doi.org/10.1038/s41416-020-01250-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007567PMC
March 2021

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.

Mol Cancer 2021 01 4;20(1). Epub 2021 Jan 4.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Background: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM.

Main Body: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis.

Conclusion: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.
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http://dx.doi.org/10.1186/s12943-020-01288-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784348PMC
January 2021

Correction: MiR-101 reverses the hypomethylation of the LMO3 promoter in glioma cells.

Oncotarget 2020 Dec 8;11(49):4605-4606. Epub 2020 Dec 8.

Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China.

[This corrects the article DOI: 10.18632/oncotarget.3181.].
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http://dx.doi.org/10.18632/oncotarget.27716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733623PMC
December 2020

The biogenesis and roles of extrachromosomal oncogene involved in carcinogenesis and evolution.

Am J Cancer Res 2020 1;10(11):3532-3550. Epub 2020 Nov 1.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha 410013, Hunan, China.

More and more extrachromosomal DNA (ecDNA) was found in human tumor cells in recent years, which has a high copy number in tumors and changes the expression of oncogenes, thus different from normal chromosomal DNA. These circular structures were identified to originate from chromosomes, and play critical roles in rapid carcinogenesis, tumor evolution and multidrug resistance. Therefore, this review mostly focuses on the biogenesis and regulation of extrachromosomal oncogene in ecDNA as well as its function and mechanism in tumors, which are of great significance for our comprehensive understanding of the role of ecDNA in tumor carcinogenic mechanism and are expected to provide ecDNA with the potential to be a new molecular target for the diagnosis and treatment of tumors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716155PMC
November 2020

LncRNA LINC00472 regulates cell stiffness and inhibits the migration and invasion of lung adenocarcinoma by binding to YBX1.

Cell Death Dis 2020 11 3;11(11):945. Epub 2020 Nov 3.

Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

There is increasing evidence that long non-coding RNAs (lncRNAs) play important roles in human tumorigenesis. By using publicly available expression profiling data from lung adenocarcinoma and integrating bioinformatics analysis, we screened a lncRNA, LINC00472. LINC00472 expression in lung adenocarcinoma tissues was significantly lower and tightly associated with patient prognosis and TNM clinical stages in lung adenocarcinoma. LINC00472 also inhibited lung adenocarcinoma cell migration and invasion and increased cell stiffness and adhesion. RNA pull down and RIP assays identified that LINC00472 interacted with the transcription factor Y-box binding protein 1 (YBX1), which partially reversed the inhibition of cell migration and invasion and increased LINC00472-induced cell stiffness and adhesion. LINC00472 also regulated the density and integrity of F-actin in A549 and PC-9 cells possibly via YBX1. LINC00472 inhibited the cell epithelial-mesenchymal transition (EMT) processes via the modulation of YBX1. These results indicated that LINC00472 inhibited the cell EMT process by binding to YBX1, and affected the mechanical properties of the cell, ultimately inhibited its ability to invade and metastasize. Collectively, the present study provides the first evidence that LINC00472 changes the mechanical properties and inhibits the invasion and metastasis of lung adenocarcinoma cells.
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http://dx.doi.org/10.1038/s41419-020-03147-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609609PMC
November 2020

Overexpression of LINC00852 promotes prostate cancer cell proliferation and metastasis.

Asia Pac J Clin Oncol 2020 Oct 30. Epub 2020 Oct 30.

Department of Oncology, Tongji Hospital of Tongji University, Shanghai, China.

Aim: Long noncoding RNAs play a key role in the development and progression of various human cancers. Recently, LINC00852 has been reported to be associated with spinal metastasis lung adenocarcinoma. However, the role and potential mechanisms of LINC00852 in prostate cancer cells remain largely unknown.

Methods: LINC00852 expression in prostate cancer cells was examined by quantitative real-time polymerase chain reaction. Western blotting was used to detect protein expressions in prostate cancer cells. Cell cycle was analyzed by flow cytometric analysis. Cell proliferation was measured by cck-8 assay. The migration and invasion capabilities were determined using transwell assays.

Results: In this study, we found that LINC00852 was highly expressed in prostate cancer tissues based on the TCGA database. Overexpression of LINC00852 mediated by lentivirus significantly reinforced the proliferation and colony formation abilities of prostate cancer cell linePC3. The migration and invasion capabilities were also augmented by overexpression of LINC00852. Flow cytometric analysis revealed that LINC00852 overexpression resulted in a decrease of cells in G0/G1 phase. Moreover, overexpression of LINC00852 affected the expression of epithelial-mesenchymal transition-related proteins.

Conclusions: Our data collectively demonstrate that LINC00852 contributes to prostate cancer proliferation and metastasis, indicating that LINC00852is a new promising diagnostic and therapeutic target for treatment of prostate cancer.
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http://dx.doi.org/10.1111/ajco.13418DOI Listing
October 2020

circSETD3 regulates MAPRE1 through miR-615-5p and miR-1538 sponges to promote migration and invasion in nasopharyngeal carcinoma.

Oncogene 2021 01 29;40(2):307-321. Epub 2020 Oct 29.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Circular RNAs (circRNAs) play an essential role in tumorigenesis and development. However, they have rarely been investigated in nasopharyngeal carcinoma (NPC). This study aimed to investigate the role of circRNA in the invasion and metastasis of NPC. We screened and verified the high expression of circSETD3 in NPC cell lines using RNA sequencing (RNA-Seq) and verified the results of NPC biopsy samples using real-time quantitative polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). In vivo and in vitro experiments indicated that circSETD3 could promote NPC cell invasion and migration. We compared the proteomic data of NPC cells before and after the overexpression or knockdown of circSETD3 in combination with bioinformatics prediction and experimental verification. It was found that circSETD3 competitively adsorbs to miR-615-5p and miR-1538 and negates their inhibitory effect on MAPRE1 mRNA, thereby upregulating the expression of MAPRE1. The upregulated MAPRE1 then inhibits the acetylation of α-tubulin, promotes the dynamic assembly of microtubules, and enhances the invasion and migration capabilities of NPC cells. The results of this study suggest that circSETD3 is a novel molecular marker and a potential target for NPC diagnosis and treatment.
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http://dx.doi.org/10.1038/s41388-020-01531-5DOI Listing
January 2021

EBV-miR-BART12 accelerates migration and invasion in EBV-associated cancer cells by targeting tubulin polymerization-promoting protein 1.

FASEB J 2020 12 23;34(12):16205-16223. Epub 2020 Oct 23.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Epstein-Barr virus (EBV) infection leads to cancers with an epithelial origin, such as nasopharyngeal cancer and gastric cancer, as well as multiple blood cell-based malignant tumors, such as lymphoma. Interestingly, EBV is also the first virus found to carry genes encoding miRNAs. EBV encodes 25 types of pre-miRNAs which are finally processed into 44 mature miRNAs. Most EBV-encoded miRNAs were found to be involved in the occurrence and development of EBV-related tumors. However, the function of EBV-miR-BART12 remains unclear. The findings of the current study revealed that EBV-miR-BART12 binds to the 3'UTR region of Tubulin Polymerization-Promoting Protein 1 (TPPP1) mRNA and downregulates TPPP1, thereby promoting the invasion and migration of EBV-related cancers, such as nasopharyngeal cancer and gastric cancer. The mechanism underlying this process was found to be the inhibition of TPPP1 by EBV-miRNA-BART12, which, in turn, inhibits the acetylation of α-tubulin, and promotes the dynamic assembly of microtubules, remodels the cytoskeleton, and enhances the acetylation of β-catenin. β-catenin activates epithelial to mesenchymal transition (EMT). These two processes synergistically promote the invasion and metastasis of tumor cells. To the best of our knowledge, this is the first study to reveal the role of EBV-miRNA-BART12 in the development of EBV-related tumors as well as the mechanism underlying this process, and suggests potential targets and strategies for the treatment of EBV-related tumors.
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http://dx.doi.org/10.1096/fj.202001508RDOI Listing
December 2020

The role of microenvironment in tumor angiogenesis.

J Exp Clin Cancer Res 2020 Sep 30;39(1):204. Epub 2020 Sep 30.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment-composed of tumor cells, surrounding cells, and secreted cytokines-provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome.
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http://dx.doi.org/10.1186/s13046-020-01709-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526376PMC
September 2020

Chronic Stress Promotes Cancer Development.

Front Oncol 2020 19;10:1492. Epub 2020 Aug 19.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Stress is an inevitable part of life. Chronic stress on account of reasons like adversity, depression, anxiety, or loneliness/social isolation can endanger human health. Recent studies have shown that chronic stress can induce tumorigenesis and promote cancer development. This review describes the latest progress of research on the molecular mechanisms by which chronic stress promotes cancer development. Primarily, chronic stress activates the classic neuroendocrine system [the hypothalamic-pituitary-adrenal (HPA) axis] and the sympathetic nervous system (SNS) and leads to a decline and dysfunction of the prefrontal cortex and the hippocampus under stress. Stress hormones produced during the activation of both the HPA axis and the SNS can promote tumorigenesis and cancer development through a variety of mechanisms. Chronic stress can also cause corresponding changes in the body's immune function and inflammatory response, which is significant because a long-term inflammatory response and the decline of the body's immune surveillance capabilities are implicated in tumorigenesis. Stress management is essential for both healthy people and cancer patients. Whether drugs that limit the signaling pathways downstream of the HPA axis or the SNS can suppress chronic stress-induced cancers or prolong patient survival deserves further study.
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http://dx.doi.org/10.3389/fonc.2020.01492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466429PMC
August 2020

Upregulation of long non-coding RNA LOC284454 may serve as a new serum diagnostic biomarker for head and neck cancers.

BMC Cancer 2020 Sep 24;20(1):917. Epub 2020 Sep 24.

Department of Stomatology, NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, No.88 Xiangya Road, Changsha, Hunan, P. R. China, 410078.

Background: Identification of effective diagnostic and prognostic biomarkers of cancer is necessary for improving precision medicine. Long non-coding RNAs (lncRNAs) play an important regulatory role in tumor initiation and progression. The lncRNA LOC284454 is distinctly expressed in various head and neck cancers (HNCs), as demonstrated by our previous bioinformatics analysis. However, the expression levels and functions of LOC284454 in cancer are still unclear.

Methods: We investigated the dysregulation of lncRNAs in HNCs using the GEO database and found that LOC284454 was highly expressed in HNCs. Serum samples from 212 patients with HNCs and 121 normal controls were included in this biomarker study. We measured the expression of LOC284454 in the sera of HNC patients and normal controls using RT-qPCR. Receiver operating characteristics (ROC) analysis is an important statistical method that is widely used in clinical diagnosis and disease screening. ROC was used to analyze the clinical value of LOC284454 in the early diagnosis of HNCs.

Results: LOC284454 was significantly upregulated in the sera of patients with nasopharyngeal carcinoma, oral cancer, and thyroid cancer. LOC284454 upregulation had good clinical diagnostic value in these cancers, as evaluated by area under the ROC curve values of 0.931, 0.698, and 0.834, respectively.

Conclusions: LOC284454 may be a valuable serum biomarker for HNCs facilitating the early diagnosis of malignant cancers. Further studies are needed to elucidate the mechanisms underlying the involvement of LOC284454 in HNCs. This study provides the first evidence that LOC284454 may be a serum biomarker for HNCs.
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http://dx.doi.org/10.1186/s12885-020-07408-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517628PMC
September 2020

CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling.

Cancer Lett 2021 01 12;496:41-56. Epub 2020 Sep 12.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, PR China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. Electronic address:

An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in malignant tumor initiation and progression; however, many circRNAs are yet unidentified, and the role of circRNAs in nasopharyngeal carcinoma (NPC) is unclear. Using RNA sequencing, we discovered a novel circRNA, termed circARHGAP12, that was processed from the pre-mRNA of the ARHGAP12 gene. CircARHGAP12 was significantly upregulated in NPC tissues and cell lines and promoted NPC cell migration and invasion. Overexpression or knockdown experiments revealed that circARHGAP12 regulates the expression of cytoskeletal remodeling-related proteins EZR, TPM3, and RhoA. CircARHGAP12 was found to bind directly to the 3' UTR of EZR mRNA and promote its stability; moreover, EZR protein interacted with TPM3 and RhoA and formed a complex to promote NPC cell invasion and metastasis. This study identified the novel circRNA circARHGAP12, characterized its biological function and mechanism, and increased our understanding of circRNAs in NPC pathogenesis. In particular, circARHGAP12 was found to promote the malignant biological phenotype of NPC via cytoskeletal remodeling, thus providing a clue for targeted therapy of NPC.
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http://dx.doi.org/10.1016/j.canlet.2020.09.006DOI Listing
January 2021

Emerging role of metabolic reprogramming in tumor immune evasion and immunotherapy.

Sci China Life Sci 2021 Apr 17;64(4):534-547. Epub 2020 Aug 17.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, 410013, China.

Mounting evidence has revealed that the therapeutic efficacy of immunotherapies is restricted to a small portion of cancer patients. A deeper understanding of how metabolic reprogramming in the tumor microenvironment (TME) regulates immunity remains a major challenge to tumor eradication. It has been suggested that metabolic reprogramming in the TME may affect metabolism in immune cells and subsequently suppress immune function. Tumor cells compete with infiltrating immune cells for nutrients and metabolites. Notably, the immunosuppressive TME is characterized by catabolic and anabolic processes that are critical for immune cell function, and elevated inhibitory signals may favor cancer immune evasion. The major energy sources that supply different immune cell subtypes also undergo reprogramming. We herein summarize the metabolic remodeling in tumor cells and different immune cell subtypes and the latest advances underlying the use of metabolic checkpoints in antitumor immunotherapies. In this context, targeting both tumor and immune cell metabolic reprogramming may enhance therapeutic efficacy.
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http://dx.doi.org/10.1007/s11427-019-1735-4DOI Listing
April 2021

Neutrophils: Accomplices in metastasis.

Cancer Lett 2020 11 31;492:11-20. Epub 2020 Jul 31.

Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China. Electronic address:

Metastasis is a critical cause of treatment failure and death in patients with advanced malignancies. Tumor cells can leave the primary site and enter the bloodstream; these circulating tumor cells then colonize target organs by overcoming blood shear stress, evading immune surveillance, and silencing the offensive capabilities of immune cells, eventually forming metastatic foci. From leaving the primary focus to the completion of distant metastasis, malignant tumor cells are supported and/or antagonized by certain immune cells. In particular, it has been found that myeloid granulocytes play an important role in this process. This review therefore aims to comprehensively describe the significance of neutrophils in solid tumor metastasis in terms of their supporting role in initiating the invasion and migration of tumor cells and assisting the colonization of circulating tumor cells in distant target organs, with the hope of providing insight into and ideas for anti-tumor metastasis treatment of tumor patients.
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http://dx.doi.org/10.1016/j.canlet.2020.07.028DOI Listing
November 2020

Upregulation of cyclin D1 can act as an independent prognostic marker for longer survival time in human nasopharyngeal carcinoma.

J Clin Lab Anal 2020 Aug 22;34(8):e23298. Epub 2020 Jul 22.

Department of Medical Laboratory Science, The Third Xiangya Hospital, Central South University, Changsha, China.

Background: Cyclin D1 is an essential part of oncogenic transformation. We previously proved that cyclin D1 was upregulated in nasopharyngeal carcinoma (NPC) and promoted the NPC cell proliferation. But the association between cyclin D1 and the clinical outcome of NPC has not yet been determined. The study explores the possible relevance between the cyclin D1 expression and clinical parameters and its predictive value of prognosis in NPC patients.

Methods: We analyzed the clinical data from 379 NPC patients and 112 non-NPC patients in our previous study, which made further statistics. Receiver operating curve (ROC) was applied to select the optimal cutoff points. By analyzing the clinical data from 101 NPC patients using Chi-squared test, we estimated the relationship between the cyclin D1 expression level and clinicopathological parameters. We also used Kaplan-Meier method and log-rank test assess and compared the disease-free survival (DFS) rate and overall survival (OS) rate. The Cox proportional hazards model was adopted to perform the univariate and multivariate analyses.

Result: Receiver operating curve analysis reported that cyclin D1 was used to differentiate between NPC patients and non-NPC patients (P < .001, sensitivity: 53.6%, specificity: 85.7%, AUC = 0.752). Cyclin D1 was positively correlated with lymph node metastasis (P = .015). A survival analysis of the 101 NPC patients indicated that the positive expression of cyclin D1 was predictive of a good prognosis (DFS: P = .010, OS: P = .019). Multivariate analysis showed that cyclin D1 could be used independently to predict NPC patients' prognosis (DFS: P = .038).

Conclusion: The overexpression of cyclin D1 is a good prognostic marker for NPC.
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http://dx.doi.org/10.1002/jcla.23298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439355PMC
August 2020

Metabolic crosstalk in the tumor microenvironment regulates antitumor immunosuppression and immunotherapy resisitance.

Cell Mol Life Sci 2021 Jan 11;78(1):173-193. Epub 2020 Jul 11.

Department of Stomatology, NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, 410078, China.

The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. In addition, tumor-derived metabolites regulate the activation and effector function of immune cells through a variety of mechanisms; in turn, the metabolites and other factors secreted by immune cells can also become accomplices to cancer development. Immune-metabolic checkpoint regulation is an emerging concept that is being studied with the aim of restoring the immune response in the tumor microenvironment. In this review, we summarize the metabolic reprogramming of various cell types present in the tumor microenvironment, with a focus on the interaction between the metabolic pathways of these cells and antitumor immunosuppression. We also discuss the main metabolic checkpoints that could provide new means of enhancing antitumor immunotherapy.
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http://dx.doi.org/10.1007/s00018-020-03581-0DOI Listing
January 2021