5,498 results match your criteria elongation cancer


Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration.

EMBO J 2021 May 5:e105770. Epub 2021 May 5.

Epithelial Biology Laboratory, Francis Crick Institute, London, UK.

Wnt signalling induces a gradient of stem/progenitor cell proliferation along the crypt-villus axis of the intestine, which becomes expanded during intestinal regeneration or tumour formation. The YAP transcriptional co-activator is known to be required for intestinal regeneration, but its mode of regulation remains controversial. Here we show that the YAP-TEAD transcription factor is a key downstream effector of Wnt signalling in the intestine. Read More

View Article and Full-Text PDF

Cordycepin inhibits the proliferation of malignant peripheral nerve sheath tumor cells through the p53/Sp1/tubulin pathway.

Am J Cancer Res 2021 15;11(4):1247-1266. Epub 2021 Apr 15.

Institute for Systems Biology Seattle, Washington, USA.

Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. In addition to skin pigmentation and cutaneous neurofibroma, some patients developed the plexiform neurofibroma since birth. Plexiform neurofibroma has abundant Schwann cells, fibroblasts, mast cells, blood vessels, and connective tissues, which increases the risk of developing a malignant peripheral nerve sheath tumor (MPNST). Read More

View Article and Full-Text PDF

Human Cytomegalovirus Uses a Host Stress Response To Balance the Elongation of Saturated/Monounsaturated and Polyunsaturated Very-Long-Chain Fatty Acids.

mBio 2021 May 4;12(3). Epub 2021 May 4.

Department of Immunobiology, University of Arizona, Tucson, Arizona, USA

Stress and virus infection regulate lipid metabolism. Human cytomegalovirus (HCMV) infection induces fatty acid (FA) elongation and increases the abundance of lipids with very-long-chain FA (VLCFA) tails. While reprogramming of metabolism can be stress related, the role of stress in HCMV reprogramming of lipid metabolism is poorly understood. Read More

View Article and Full-Text PDF

New Quinolinone O-GlcNAc Transferase Inhibitors Based on Fragment Growth.

Front Chem 2021 14;9:666122. Epub 2021 Apr 14.

The Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.

O-GlcNAcylation is an important post-translational and metabolic process in cells that must be carefully regulated. O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to proteins. OGT is a promising target in various pathologies such as cancer, immune system diseases, or nervous impairment. Read More

View Article and Full-Text PDF

Cancer-associated POT1 mutations lead to telomere elongation without induction of a DNA damage response.

EMBO J 2021 May 2:e107346. Epub 2021 May 2.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.

Mutations in the shelterin protein POT1 are associated with chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, angiosarcoma, melanoma, and other cancers. These cancer-associated POT1 (caPOT1) mutations are generally heterozygous, missense, or nonsense mutations occurring throughout the POT1 reading frame. Cancers with caPOT1 mutations have elongated telomeres and show increased genomic instability, but which of the two phenotypes promotes tumorigenesis is unclear. Read More

View Article and Full-Text PDF

Case Report: Blurred Vision and Eruptive Nevi - Bilateral Diffuse Uveal Melanocytic Proliferation With Mucocutaneous Involvement in a Lung Cancer Patient.

Front Oncol 2021 13;11:658407. Epub 2021 Apr 13.

Eye Center, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Read More

View Article and Full-Text PDF

Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis.

Cancers (Basel) 2021 Apr 14;13(8). Epub 2021 Apr 14.

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore.

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. Read More

View Article and Full-Text PDF

Novel role of CAP1 in regulation RNA polymerase II-mediated transcription elongation depends on its actin-depolymerization activity in nucleoplasm.

Oncogene 2021 Apr 28. Epub 2021 Apr 28.

Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, Chongqing, China.

Lung cancer is one of the most intractable diseases with high incidence and mortality worldwide. Adenylate cyclase-associated protein 1 (CAP1), a well-known actin depolymerization factor, is recently reported to be an oncogene accelerating cancer cell proliferation. However, the physiological significance of CAP1 in lung cancer is incompletely understood and the novel functions of CAP1 in transcriptional regulation remain unknown. Read More

View Article and Full-Text PDF

Inhibition of eEF2K synergizes with glutaminase inhibitors or 4EBP1 depletion to suppress growth of triple-negative breast cancer cells.

Sci Rep 2021 Apr 28;11(1):9181. Epub 2021 Apr 28.

Max Bell Research Centre, Toronto General Research Institute, University Health Network, 101 College Street, Suite 5R406, Toronto, ON, M5G 1L7, Canada.

The eukaryotic elongation factor-2 kinase, eEF2K, which restricts protein translation elongation, has been identified as a potential therapeutic target for diverse types of malignancies including triple negative breast cancer (TNBC). However, the contexts in which eEF2K inhibition is essential in TNBC and its consequences on the proteome are largely unknown. Here we show that genetic or pharmacological inhibition of eEF2K cooperated with glutamine (Gln) starvation, and synergized with glutaminase (GLS1) inhibitors to suppress growth of diverse TNBC cell lines. Read More

View Article and Full-Text PDF

Transcription-coupled nucleotide excision repair: New insights revealed by genomic approaches.

DNA Repair (Amst) 2021 Apr 20;103:103126. Epub 2021 Apr 20.

Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, 87131, USA. Electronic address:

Elongation of RNA polymerase II (Pol II) is affected by many factors including DNA damage. Bulky damage, such as lesions caused by ultraviolet (UV) radiation, arrests Pol II and inhibits gene transcription, and may lead to genome instability and cell death. Cells activate transcription-coupled nucleotide excision repair (TC-NER) to remove Pol II-impeding damage and allow transcription resumption. Read More

View Article and Full-Text PDF

Protein phosphatases in the RNAPII transcription cycle: erasers, sculptors, gatekeepers, and potential drug targets.

Genes Dev 2021 May 22;35(9-10):658-676. Epub 2021 Apr 22.

Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

The transcription cycle of RNA polymerase II (RNAPII) is governed at multiple points by opposing actions of cyclin-dependent kinases (CDKs) and protein phosphatases, in a process with similarities to the cell division cycle. While important roles of the kinases have been established, phosphatases have emerged more slowly as key players in transcription, and large gaps remain in understanding of their precise functions and targets. Much of the earlier work focused on the roles and regulation of sui generis and often atypical phosphatases-FCP1, Rtr1/RPAP2, and SSU72-with seemingly dedicated functions in RNAPII transcription. Read More

View Article and Full-Text PDF

Technical considerations depending on the level of vascular ligation in laparoscopic rectal resection.

Surg Endosc 2021 Apr 19. Epub 2021 Apr 19.

Department of Surgery, University Hospital Alexandrovska, Sofia, St. Georgi Sofiyski Str. 1, 1431, Sofia, Bulgaria.

Aim: In addition to ischemia there is also anastomotic ends tension proven to be a risk factor for anastomotic leak. HT vascular ligation is accepted as a rule, in attempt to achieve tension-free anastomosis. LT is a preferred option, based on the more accurate preservation of proximal intestinal segment microperfusion and lower risk of damage to the hypogastric plexus. Read More

View Article and Full-Text PDF

COMMD4 functions with the histone H2A-H2B dimer for the timely repair of DNA double-strand breaks.

Commun Biol 2021 Apr 19;4(1):484. Epub 2021 Apr 19.

Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba, QLD, Australia.

Genomic stability is critical for normal cellular function and its deregulation is a universal hallmark of cancer. Here we outline a previously undescribed role of COMMD4 in maintaining genomic stability, by regulation of chromatin remodelling at sites of DNA double-strand breaks. At break-sites, COMMD4 binds to and protects histone H2B from monoubiquitination by RNF20/RNF40. Read More

View Article and Full-Text PDF

A Cooperatively Activatable, DNA-based Fluorescent Reporter for Imaging of Correlated Enzymatic Activities.

Angew Chem Int Ed Engl 2021 Apr 19. Epub 2021 Apr 19.

National Center for Nanoscience and Technology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, 11 ZhongGuanCun BeiYiTiao, Haidian District, 100190, Beijing, CHINA.

The dynamic variation of the expression profile and spatial landscape of multiple enzymes are crucial factors influencing tumor progression and drug treatment. However, the comprehensive analysis of these events has been hampered by the limitations of existing imaging technologies. Here we reported a cooperatively activatable, DNA-based fluorescent reporter programmed to detect the correlated activity of dual enzymes, telomerase (TE) and apurinic/apyrimidinic endonuclease 1 (APE1), both in vitro and in vivo. Read More

View Article and Full-Text PDF

Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer Growth .

ACS Pharmacol Transl Sci 2021 Apr 30;4(2):926-940. Epub 2021 Mar 30.

Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, Texas 77030, United States.

Eukaryotic elongation factor 2 kinase (eEF-2K) is an unusual alpha kinase involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is highly overexpressed in breast cancer, and its activity is associated with significantly shortened patient survival and proven to be a potential molecular target in breast cancer. The crystal structure of eEF-2K remains unknown, and there is no potent, safe, and effective inhibitor available for clinical applications. Read More

View Article and Full-Text PDF

Differential Expression Profiles and Function Prediction of Transfer RNA-Derived Fragments in High-Grade Serous Ovarian Cancer.

Biomed Res Int 2021 30;2021:5594081. Epub 2021 Mar 30.

Department of Gynecology, Huangshi Love & Health Hospital Affiliated to Hubei Polytechnic University, Huangshi, 435000 Hubei, China.

Background: The present study is aimed at providing systematic insight into the composition and expression of transfer RNA (tRNA) derivative transcription in high-grade serous ovarian cancer (HGSOC).

Methods: tRNA derivative expression profiles in three pairs of HGSOC and adjacent normal ovarian tissues were conducted by tRNA-derived small RNA fragment (tRF) and tRNA half (tiRNA) sequencing. The differentially expressed tRFs and tiRNAs between HGSOC and paired adjacent normal samples were screened. Read More

View Article and Full-Text PDF

Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.

Nat Commun 2021 04 15;12(1):2170. Epub 2021 Apr 15.

Laboratory of Cancer Signaling, University of Liège, Liège, Belgium.

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcms wobble uridine tRNA modification (U-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. Read More

View Article and Full-Text PDF

Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing.

Cell Rep 2021 Apr;35(2):108977

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla 41092, Spain; Topology and DNA Breaks Group, Spanish National Cancer Centre (CNIO), Madrid 28029, Spain. Electronic address:

Accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered positive facilitators of transcription. Here, we show that, in contrast to this general assumption, human topoisomerase IIα (TOP2A) activity at promoters represses transcription of immediate early genes such as c-FOS, maintaining them under basal repressed conditions. Read More

View Article and Full-Text PDF

Diagnostic value of MDCT in determining the perinephric fat tissue and renal sinus invasion in patients with clear cell renal cell carcinoma.

Niger J Clin Pract 2021 Apr;24(4):489-495

Lutfi Kirdar Kartal Education and Research Hospital, Cevizli mh. Şemsi Denizer cad. E-5 Karayolu Cevizli Mevkii, 34890 Kartal, İstanbul, Turkey.

Aims: To investigate the accuracy of multidetector computed tomography (MDCT) findings, and the effect of tumor volume in determining the perinephric and renal sinus invasion in clear cell renal cell carcinomas (ccRCCs).

Method: Fifty patients with ccRCCs underwent non-contrast and nephrographic-phase contrast-enhanced MDCT examination before total nephrectomy. The following MDCT features were used to diagnose perinephric fat tissue invasion: perinephric stranding, perinephric vascularity, and irregular contour. Read More

View Article and Full-Text PDF

Nannocystin Ax, a natural elongation factor 1α inhibitor from Nannocystis sp., suppresses epithelial-mesenchymal transition, adhesion and migration in lung cancer cells.

Toxicol Appl Pharmacol 2021 Jun 14;420:115535. Epub 2021 Apr 14.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address:

Epithelial-mesenchymal transition (EMT), the epithelial cells transdifferentiation into the mesenchymal cells, has been involved in cancer metastasis. Nannocystin ax (NAN) is a cyclodepsipeptide initially isolated from Myxobacterial genus, Nannocystis sp. with anticancer activities. Read More

View Article and Full-Text PDF

Cervical elongation caused by big cervical fibroid resembling malignant cervical prolapse? Management via vaginal surgery.

Int J Surg Case Rep 2021 Mar 29;82:105847. Epub 2021 Mar 29.

Urogynecology Division Department of Obstetrics and Gynecology, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

Introduction: Cervical elongation could lead to cervical elongation thus worsen the descent of uterine prolapse. In certain cases, this hypertrophic and hyperplastic mass could have fragile surface with some bleeding and necrotic, resembling cervical cancer. As case of cervical elongation due to cervical fibroid is quite rare, such cases are valuable to be reported. Read More

View Article and Full-Text PDF

Peptidoglycan Recognition Peptide 2 Aggravates Weight Loss in a Murine Model of Chemotherapy-Induced Gastrointestinal Toxicity.

Front Oncol 2021 23;11:635005. Epub 2021 Mar 23.

Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

Chemotherapy-induced gastrointestinal toxicity (CIGT) is a frequent, severe and dose-limiting side effect. Few treatments have proven effective for CIGT. CIGT is characterized by activation of the nuclear factor kappa B pathway which, leads to upregulation of proinflammatory cytokines. Read More

View Article and Full-Text PDF

Single molecule network analysis identifies structural changes to caveolae and scaffolds due to mutation of the caveolin-1 scaffolding domain.

Sci Rep 2021 Apr 8;11(1):7810. Epub 2021 Apr 8.

Life Sciences Institute, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.

Caveolin-1 (CAV1), the caveolae coat protein, also associates with non-caveolar scaffold domains. Single molecule localization microscopy (SMLM) network analysis distinguishes caveolae and three scaffold domains, hemispherical S2 scaffolds and smaller S1B and S1A scaffolds. The caveolin scaffolding domain (CSD) is a highly conserved hydrophobic region that mediates interaction of CAV1 with multiple effector molecules. Read More

View Article and Full-Text PDF

The Intraflagellar Transport Protein IFT20 Recruits ATG16L1 to Early Endosomes to Promote Autophagosome Formation in T Cells.

Front Cell Dev Biol 2021 22;9:634003. Epub 2021 Mar 22.

Department of Life Sciences, University of Siena, Siena, Italy.

Lymphocyte homeostasis, activation and differentiation crucially rely on basal autophagy. The fine-tuning of this process depends on autophagy-related (ATG) proteins and their interaction with the trafficking machinery that orchestrates the membrane rearrangements leading to autophagosome biogenesis. The underlying mechanisms are as yet not fully understood. Read More

View Article and Full-Text PDF

Structure of TFIIK for phosphorylation of CTD of RNA polymerase II.

Sci Adv 2021 Apr 7;7(15). Epub 2021 Apr 7.

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

During transcription initiation, the general transcription factor TFIIH marks RNA polymerase II by phosphorylating Ser5 of the carboxyl-terminal domain (CTD) of Rpb1, which is followed by extensive modifications coupled to transcription elongation, mRNA processing, and histone dynamics. We have determined a 3.5-Å resolution cryo-electron microscopy (cryo-EM) structure of the TFIIH kinase module (TFIIK in yeast), which is composed of Kin28, Ccl1, and Tfb3, yeast homologs of CDK7, cyclin H, and MAT1, respectively. Read More

View Article and Full-Text PDF

Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis.

Int J Mol Sci 2021 Mar 22;22(6). Epub 2021 Mar 22.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.

The occurrence of distant tumor metastases is a major barrier in non-small cell lung cancer (NSCLC) therapy, and seriously affects clinical treatment and patient prognosis. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to be crucial regulators of metastasis in lung cancer. The aim of this study was to reveal the underlying mechanisms of a novel lncRNA LNC CRYBG3 in regulating NSCLC metastasis. Read More

View Article and Full-Text PDF

The Winged Helix Domain of CSB Regulates RNAPII Occupancy at Promoter Proximal Pause Sites.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada.

Cockayne syndrome group B protein (CSB), a member of the SWI/SNF superfamily, resides in an elongating RNA polymerase II (RNAPII) complex and regulates transcription elongation. CSB contains a C-terminal winged helix domain (WHD) that binds to ubiquitin and plays an important role in DNA repair. However, little is known about the role of the CSB-WHD in transcription regulation. Read More

View Article and Full-Text PDF

The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin.

Life (Basel) 2021 Mar 24;11(4). Epub 2021 Mar 24.

Faculty of Medicine Nice, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, Université Côte d'Azur, 06107 Nice, France.

Heterochromatic regions render the replication process particularly difficult due to the high level of chromatin compaction and the presence of repeated DNA sequences. In humans, replication through pericentromeric heterochromatin requires the binding of a complex formed by the telomeric factor TRF2 and the helicase RTEL1 in order to relieve topological barriers blocking fork progression. Since TRF2 is known to bind the Origin Replication Complex (ORC), we hypothesized that this factor could also play a role at the replication origins (ORI) of these heterochromatin regions. Read More

View Article and Full-Text PDF

Arsenic uptake and toxicity in wheat (Triticum aestivum L.): A review of multi-omics approaches to identify tolerance mechanisms.

Food Chem 2021 Sep 18;355:129607. Epub 2021 Mar 18.

Environmental Health and Ecotoxicology Laboratory, Department of Environmental Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address:

Arsenic (As) due to its widespread has become a primary concern for sustainable food production, especially in Southeast Asian countries. In that context, the present review presented a comprehensive detail of the available literature marking an assortment of As-induced impacts on wheat. The conclusive findings of past research suggest that As tends to grossly affect the germination, elongation, biomass, grain yield, and induce oxidative stress. Read More

View Article and Full-Text PDF
September 2021