906,049 results match your criteria cell signaling

AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma.

J Exp Med 2021 Sep 29;218(9). Epub 2021 Jul 29.

Department of Dermatology, University of Massachusetts Medical School, Worcester, MA.

The STING and absent in melanoma 2 (AIM2) pathways are activated by the presence of cytosolic DNA, and STING agonists enhance immunotherapeutic responses. Here, we show that dendritic cell (DC) expression of AIM2 within human melanoma correlates with poor prognosis and, in contrast to STING, AIM2 exerts an immunosuppressive effect within the melanoma microenvironment. Vaccination with AIM2-deficient DCs improves the efficacy of both adoptive T cell therapy and anti-PD-1 immunotherapy for "cold tumors," which exhibit poor therapeutic responses. Read More

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September 2021

PDIA6 promotes pancreatic cancer progression and immune escape through CSN5-mediated deubiquitination of β-catenin and PD-L1.

Neoplasia 2021 Jul 26;23(9):912-928. Epub 2021 Jul 26.

Department of Pathophysiology, Zhengzhou University, Zhengzhou, China.

Protein Disulfide Isomerase Family A Member 6 (PDIA6) is an endoplasmic reticulum protein that is capable of catalyzing protein folding and disulfide bond formation. Abnormally elevated expression of PDIA6 has been reported to predict poor outcomes in various cancers. Herein, gain-of- and loss-of-function experiments were performed to investigate how PDIA6 participated in the carcinogenesis of pancreatic cancer (PC). Read More

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Simultaneous inhibition of PFKFB3 and GLS1 selectively kills KRAS-transformed pancreatic cells.

Biochem Biophys Res Commun 2021 Jul 26;571:118-124. Epub 2021 Jul 26.

Department of Biochemistry, School of Veterinary Medicine, Bursa Uludag University, Bursa, 16059, Turkey. Electronic address:

Activating mutations of the oncogenic KRAS in pancreatic ductal adenocarcinoma (PDAC) are associated with an aberrant metabolic phenotype that may be therapeutically exploited. Increased glutamine utilization via glutaminase-1 (GLS1) is one such feature of the activated KRAS signaling that is essential to cell survival and proliferation; however, metabolic plasticity of PDAC cells allow them to adapt to GLS1 inhibition via various mechanisms including activation of glycolysis, suggesting a requirement for combinatorial anti-metabolic approaches to combat PDAC. We investigated whether targeting the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) in combination with GLS1 can selectively prevent the growth of KRAS-transformed cells. Read More

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Role of IL-6 in the commitment of T cell subsets.

Cytokine 2021 Jul 26;146:155654. Epub 2021 Jul 26.

Institute for Experimental Neuroimmunology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.

IL-6 gained much attention with the discovery that this cytokine is a non-redundant differentiation factor for Th17 cells and T follicular helper cells. Adaptive immune responses to fungi and extracellular bacteria are impaired in the absence of IL-6. IL-6 is also required for the induction of ROR-γt Treg cells, which are gatekeepers of homeostasis in the gut lamina propria in the presence of commensal bacteria. Read More

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Interleukin 27 as an inducer of antiviral response against chikungunya virus infection in human macrophages.

Cell Immunol 2021 Jul 21;367:104411. Epub 2021 Jul 21.

Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. Electronic address:

Chikungunya virus (CHIKV) is known to have a wide range of tropism in human cell types throughout infection, including keratinocytes, fibroblasts, endothelial cells, monocytes, and macrophages. We reported that human monocytes-derived macrophages (MDMs) are permissive to CHIKV infection in vitro. We found that the peak of CHIKV replication was at 24 hpi; however, at 48 hpi, a significant reduction in viral titer was observed that correlated with high expression levels of genes encoding antiviral proteins (AVPs) in an IFN-independent manner. Read More

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Deciphering and engineering tissue folding: a mechanical perspective.

Acta Biomater 2021 Jul 26. Epub 2021 Jul 26.

Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics, Hong Kong SAR, China. Electronic address:

The folding of tissues/organs into complex shapes is a common phenomenon that occurs in organisms such as animals and plants, and is both structurally and functionally important. Deciphering the process of tissue folding and applying this knowledge to engineer folded systems would significantly advance the field of tissue engineering. Although early studies focused on investigating the biochemical signaling events that occur during the folding process, the physical or mechanical aspects of the process have received increasing attention in recent years. Read More

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Biomaterial-based delivery of nucleic acids for tissue regeneration.

Adv Drug Deliv Rev 2021 Jul 26:113885. Epub 2021 Jul 26.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention, Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P.R.China. Electronic address:

Gene therapy is a promising novel method of tissue regeneration by stimulating or inhibiting key signaling pathways. However, their therapeutic applications in vivo are largely limited by several physiological obstacles, such as degradation of nucleases, impermeability of cell membranes, and transport to the desired intracellular compartments. Biomaterial-based gene delivery systems can overcome the problems of stability and local drug delivery, and can temporarily control the overexpression of therapeutic genes, leading to the local production of physiologically relevant levels of regulatory factors. Read More

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Role Of Epidermal Growth Factor Receptor Signaling In A Pt(Ii)-Resistant Human Breast Cancer Cell Line.

Biochem Pharmacol 2021 Jul 26:114702. Epub 2021 Jul 26.

Department of Biological and Environmental Science and Technologies (DiSTeBA), University of Salento, Via Prov. le Lecce-Monteroni, 73100 Lecce, Italy.

Platinum complexes are currently used for breast cancer therapy, but, as with other drug classes, a series of intrinsic and acquired resistance mechanisms hinder their efficacy. To better understand the mechanisms underlying platinum complexes resistance in breast cancer, we generated a [Pt(O,O'-acac)(γ-acac)(DMS)]-resistant MCF-7, denoted as [Pt(acac)]R. [Pt(O,O'-acac)(γ-acac)(DMS)] was chosen as previous works showed that it has distinct mechanisms of action from cisplatin, especially with regard to cellular targets. Read More

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Interaction between Ras and Src clones causes interdependent tumor malignancy via Notch signaling in Drosophila.

Dev Cell 2021 Jul 20. Epub 2021 Jul 20.

Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address:

Cancer tissue often comprises multiple tumor clones with distinct oncogenic alterations such as Ras or Src activation, yet the mechanism by which tumor heterogeneity drives cancer progression remains elusive. Here, we show in Drosophila imaginal epithelium that clones of Ras- or Src-activated benign tumors interact with each other to mutually promote tumor malignancy. Mechanistically, Ras-activated cells upregulate the cell-surface ligand Delta while Src-activated cells upregulate its receptor Notch, leading to Notch activation in Src cells. Read More

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Diosgenin exerts anti-tumor effects through inactivation of cAMP/PKA/CREB signaling pathway in colorectal cancer.

Eur J Pharmacol 2021 Jul 26:174370. Epub 2021 Jul 26.

Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China. Electronic address:

Colorectal cancer (CRC) is the most fatal gastrointestinal tumor and it is urge to explore powerful drugs for the treatment. Diosgenin (DSG) as a new steroidal had been reported exerts anti-tumor activity in multiple cancers, including CRC. However, the potential mechanism of DSG suppresses CRC remains further to be revealed. Read More

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Calcium signaling induces a partial EMT.

EMBO Rep 2021 Jul 29:e51872. Epub 2021 Jul 29.

Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Epithelial plasticity, or epithelial-to-mesenchymal transition (EMT), is a well-recognized form of cellular plasticity, which endows tumor cells with invasive properties and alters their sensitivity to various agents, thus representing a major challenge to cancer therapy. It is increasingly accepted that carcinoma cells exist along a continuum of hybrid epithelial-mesenchymal (E-M) states and that cells exhibiting such partial EMT (P-EMT) states have greater metastatic competence than those characterized by either extreme (E or M). We described recently a P-EMT program operating in vivo by which carcinoma cells lose their epithelial state through post-translational programs. Read More

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The role of interleukin-1β in the immune response to contact allergens.

Contact Dermatitis 2021 Jul 29. Epub 2021 Jul 29.

The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Interleukin-1β (IL-1β) is an important pro-inflammatory cytokine that has an effect on almost every cell lineage in the body. By blocking IL-1β and investigating the IL-1β signaling pathway, several studies have demonstrated a central role of IL-1β in the response to contact allergens. This review summarizes the current literature regarding the basic immunological mechanisms mediated by IL-1β in the different phases of allergic contact dermatitis (ACD) and highlights potential IL-1β-targeted treatment options, which in the future may be relevant in the treatment of patients with ACD. Read More

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Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of Drosophila germline stem cells.

Dev Growth Differ 2021 Jul 29. Epub 2021 Jul 29.

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.

The Drosophila female germline stem cell (GSC) niche provides an excellent model for understanding the stem cell niche in vivo. The GSC niche is composed of stromal cells that provide growth factors for the maintenance of GSCs and the associated extracellular matrix (ECM). Although the function of stromal cells/growth factors has been well-studied, the function of the ECM in the GSC niche is largely unknown. Read More

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Irradiation of the Normal Murine Tongue Causes Upregulation and Activation of Transient Receptor Potential (TRP) Ion Channels.

Radiat Res 2021 Jul 29. Epub 2021 Jul 29.

Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina.

Signal transduction at sensory neurons occurs via transmembrane flux of cations, which is largely governed by the transient receptor potential (TRP) family of ion channels. It is unknown whether TRP channel activation contributes to the pain that accompanies radiation-induced oral mucositis. This study sought to characterize changes in TRP channel expression and function that occur in the locally irradiated tissues and afferent neurons of mice. Read More

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The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.

PLoS One 2021 29;16(7):e0254036. Epub 2021 Jul 29.

Department of Preventive Medicine, Stony Brook University, Stony Brook, New York, United States of America.

The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. We explored the pathophysiology of DED using a rabbit model of chronic DED induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands. The transcriptome of full-thickness's conjunctival tissue from rabbits with DED and from normal controls was determined using microarrays and, as needed, confirmatory real-time polymerase chain reactions. Read More

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Inhibition of PI3K and MAPK pathways along with KIT inhibitors as a strategy to overcome drug resistance in gastrointestinal stromal tumors.

PLoS One 2021 29;16(7):e0252689. Epub 2021 Jul 29.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.

Activating mutations in KIT/PDGFRA receptor tyrosine kinases drive gastrointestinal stromal tumors (GIST). KIT/PDGFRA inhibitors, such as imatinib do not evoke an effective cytocidal response, leaving room for quiescence and development of multiple secondary resistance mutations. As the majority of the secondary resistance clones activate PI3K and MAPK pathways, we investigated whether combined targeting of KIT/PI3K/MAPK (KPM) pathways overcomes drug resistance and quiescence in GIST cells. Read More

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Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

PLoS Genet 2021 Jul 29;17(7):e1009679. Epub 2021 Jul 29.

Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.

Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. Read More

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Fibroblast-specific IKKβ deficiency ameliorates angiotensin II-induced adverse cardiac remodeling in mice.

JCI Insight 2021 Jul 29. Epub 2021 Jul 29.

Division of Biomedical Sciences, University of California, Riverside, United States of America.

Cardiac inflammation and fibrosis contribute significantly to hypertension-related adverse cardiac remodeling. IκB kinase β (IKKβ), a central coordinator of inflammation through activation of NF-κB, has been demonstrated as a key molecular link between inflammation and cardiovascular disease. However, the cell-specific contribution of IKKβ signaling towards adverse cardiac remodeling remains elusive. Read More

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Curcumin in combination with homoharringtonine suppresses lymphoma cell growth by inhibiting the TGF-β/Smad3 signaling pathway.

Aging (Albany NY) 2021 Jul 29;13(undefined). Epub 2021 Jul 29.

Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, PR China.

Both homoharringtonine (HHT) and curcumin exhibit anti-proliferative effects on lymphoma cells, but the effects of combined HHT and curcumin treatment remain unclear. Here, we investigated the effects of HHT/curcumin combination on the proliferation, apoptosis, and invasion in lymphoma cells. CCK-8, flow cytometry, and transwell assays were used to assess proliferation, apoptosis, and invasion of U937 and Raji cells. Read More

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A subset of CB002 xanthine analogs bypass p53-signaling to restore a p53 transcriptome and target an S-phase cell cycle checkpoint in tumors with mutated-p53.

Elife 2021 Jul 29;10. Epub 2021 Jul 29.

Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, United States.

Mutations in TP53 occur commonly in the majority of human tumors and confer aggressive tumor phenotypes, including metastasis and therapy resistance. CB002 and structural-analogs restore p53 signaling in tumors with mutant-p53 but we find that unlike other xanthines such as caffeine, pentoxifylline, and theophylline, they do not deregulate the G2 checkpoint. Novel CB002-analogs induce pro-apoptotic Noxa protein in an ATF3/4-dependent manner, whereas caffeine, pentoxifylline, and theophylline do not. Read More

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Artificial Taste Buds: Bioorthogonally Ligated Gustatory-Neuronal Multicellular Hybrids Enabling Intercellular Taste Signal Transmission.

ACS Biomater Sci Eng 2021 Jul 29. Epub 2021 Jul 29.

Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.

Heterogeneous tissue models require the assembly and co-culture of multiple types of cells. Our recent work demonstrated taste signal transmission from gustatory cells to neurons by grafting single-stranded DNA into the cell membrane to construct multicellular assemblies. However, the weak DNA linkage and low grafting density allowed the formation of large gustatory cell self-aggregates that cannot communicate with neurons efficiently. Read More

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The first human induced pluripotent stem cell line of Kashin-Beck disease reveals involvement of heparan sulphate proteoglycan biosynthesis and PPAR pathway.

FEBS J 2021 Jul 29. Epub 2021 Jul 29.

School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, 710061, P.R. China.

Objective: Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cells (hiPSCs) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing. Read More

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Neutral nitrogen donor ligand-based MOFs for sensing applications.

Chem Asian J 2021 Jul 29. Epub 2021 Jul 29.

IISER Pune, Chemistry, Dr. Homi Bhabha Road, Pashan, 411008, Pune, INDIA.

Neutral nitrogen donor (N-donor) ligand-based MOFs, with their enticing features inclusive of facile synthesis, labile metal-ligand bond, framework flexibility, atomic level tunability renders them appealing in molecular recognition-based studies. Intriguingly, the flexibility in such systems (owing to weaker metal-nitrogen bonds) promote maximization of host-analyte interactions, which is critical for the manifestation of a signaling response. Such host-analyte interactions can be tapped by discerning any change in the physical properties associated with the system, such as optical, fluorometric, chemiresistive, magnetic, dielectric constant, mass. Read More

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Polycystin-1 regulates cardiomyocyte mitophagy.

FASEB J 2021 Aug;35(8):e21796

Advanced Center of Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas y Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Polycystin-1 (PC1) is a transmembrane protein found in different cell types, including cardiomyocytes. Alterations in PC1 expression have been linked to mitochondrial damage in renal tubule cells and in patients with autosomal dominant polycystic kidney disease. However, to date, the regulatory role of PC1 in cardiomyocyte mitochondria is not well understood. Read More

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Live visualization of a functional RET-EGFP chimeric receptor in homozygous knock-in mice.

Dev Growth Differ 2021 Jul 29. Epub 2021 Jul 29.

Division for Neural Differentiation and Regeneration, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine.

The GDNF Family Ligands (GFLs) regulate neural development and kidney organogenesis by activating the RET receptor tyrosine kinase. Many of RET-dependent developmental processes involve long-distance cell-cell communications or cell polarity, which includes cell migration and axon guidance. This suggests that spatiotemporally regulated subcellular localization of RET protein and appropriate propagation of RET signaling in cells are essential for the physiological function of the GFLs. Read More

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Generation of Motor Neurons from Human ESCs/iPSCs Using Sendai Virus Vectors.

Methods Mol Biol 2021 ;2352:127-132

Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.

Human motor neurons are important materials for the research of the pathogenesis and drug discovery of motor neuron diseases. Various methods to generate motor neurons (MNs) from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) by the addition of signaling molecules have been reported. However, they require multiple steps and complicated processes. Read More

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January 2021

Selective Inhibition of JAK1 Primes STAT5-Driven Human Leukemia Cells for ATRA-Induced Differentiation.

Target Oncol 2021 Jul 29. Epub 2021 Jul 29.

Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA.

Background: All-trans retinoic acid (ATRA), a derivate of vitamin A, has been successfully used as a therapy to induce differentiation in M3 acute promyelocytic leukemia (APML), and has led to marked improvement in outcomes. Previously, attempts to use ATRA in non-APML in the clinic, however, have been underwhelming, likely due to persistent signaling through other oncogenic drivers. Dysregulated JAK/STAT signaling is known to drive several hematologic malignancies, and targeting JAK1 and JAK2 with the JAK1/JAK2 inhibitor ruxolitinib has led to improvement in survival in primary myelofibrosis and alleviation of vasomotor symptoms and splenomegaly in polycythemia vera and myelofibrosis. Read More

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The Metaflammatory and Immunometabolic Role of Macrophages and Microglia in Diabetic Retinopathy.

Hum Cell 2021 Jul 29. Epub 2021 Jul 29.

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Medical University Eye Hospital, No. 251, Fukang Road, Nankai District, Tianjin, 300384, China.

Emergent studies reveal the roles of inflammatory cells and cytokines in the development of diabetic retinopathy (DR), which is gradually portrayed as a chronic inflammatory disease accompanied by metabolic disorder. Through the pathogenesis of DR, macrophages or microglia play a critical role in the inflammation, neovascularization, and neurodegeneration of the retina. Conventionally, macrophages are generally divided into M1 and M2 phenotypes which mainly rely on glycolysis and oxidative phosphorylation, respectively. Read More

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Intuitive repositioning of an anti-depressant drug in combination with tivozanib: precision medicine for breast cancer therapy.

Mol Cell Biochem 2021 Jul 29. Epub 2021 Jul 29.

Precision NeuroOncology & NeuroVascular Disease Modeling Group, Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Delhi-NCR, 201314, India.

Despite the existing therapies and lack of receptors such as HER-2, estrogen receptor and progesterone receptor, triple-negative breast cancer is one of the most aggressive subtypes of breast cancer. TNBCs are known for their highly aggressive metastatic behavior and typically migrate to brain and bone for secondary site propagation. Many diseases share similar molecular pathology exposing new avenues in molecular signaling for engendering innovative therapies. Read More

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Ziziphus jujuba Mill. leaf extract restrains adipogenesis by targeting PI3K/AKT signaling pathway.

Biomed Pharmacother 2021 Jul 18;141:111934. Epub 2021 Jul 18.

Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria; Laboratory Metabolomics, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria. Electronic address:

The escalation in the global prevalence of obesity has focused attention on finding novel approaches for its management. Ziziphus jujuba Mill. (ZJL) leaf extract is reported as a traditional remedy for diverse pathological conditions, including obesity. Read More

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