Intestinal Cell News 3.34 September 8, 2017 | |
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TOP STORYPaneth Cells Secrete Lysozyme via Secretory Autophagy during Bacterial Infection of the Intestine Investigators showed that during bacterial infection, lysozyme is rerouted via secretory autophagy, an autophagy-based alternative secretion pathway. Secretory autophagy was triggered in Paneth cells by bacteria-induced endoplasmic reticulum stress, required extrinsic signals from innate lymphoid cells, and limited bacterial dissemination. [Science] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)INTESTINAL CANCERS & DISEASESResearchers report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that was termed PURPL. Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induced growth defects in cell culture and in mouse xenografts. [Cell Rep] Full Article | Graphical Abstract Scientists report that transient receptor potential channel 5 (TrpC5), a receptor-activated non-selective Ca2+ channel, was correlated with tumor metastasis in colon cancer patients. In colon cancer cells, overexpression of TrpC5 caused a robust [Ca2+]i rise, decreased E-cadherin, and increased mesenchymal biomarker expression, then promoted cell migration, invasion, and proliferation. [Clin Sci (Lond)] Abstract MicroRNA–449a Deficiency Promotes Colon Carcinogenesis The authors found that miR–449a was indirectly regulated by Notch signaling. Although miR–449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR–449a-deficient mice with azoxymethane or dextran sodium sulfate increased the numbers and sizes of colon tumors. [Sci Rep] Full Article Scientists report that MIER3 was significantly reduced in human primary colorectal cancer and was associated with colorectal cancer (CRC) metastasis and poor prognosis. The up-regulation of mesoderm induction early response 1, family member 3 (MIER3) expression significantly inhibited CRC cell proliferation, migration and invasion in vitro and repressed tumor growth and metastasis in vivo. [Sci Rep] Full Article Investigators report that HIF-2 robustly increased YAP1 expression and activity in colorectal cancer-derived cell lines and in mouse models. The potentiation of YAP1 activity by HIF-2 was not via canonical signaling mechanisms, such as Src, PI3K, ERK, or MAPK pathways. Moreover, they detected no direct interaction of HIF-2 with YAP1. [J Biol Chem] Abstract | Full Article VEGFR2 Regulates Endothelial Differentiation of Colon Cancer Cells After culturing in endothelial-inducing conditioned medium, poorly differentiated HCT116 cells expressed endothelial markers and formed tube-like structure in vitro. HCT116 cells secreted more endogenous VE growth factor (VEGF) and expressed higher VEGF receptor 2 (VEGFR2) under hypoxia. [BMC Cancer] Full Article INTESTINAL STEM CELL & ORGANOID RESEARCHThe authors showed that miR–31 drives intestinal stem cell (ISC) proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Mechanistically, miR–31 acted to balance input from Wnt, BMP, TGFβ signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. [eLife] Full Article Two fluorescent biosensors were developed based on human-induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters (KLF5mCherry and ISXeGFP). Human intestinal organoids were efficiently induced from those transgenic hiPSC lines in which monomeric Cherry– or enhanced green fluorescent protein–expressing cells, which appeared during differentiation, could be identified in intact living cells in real time. [FASEB J] Abstract | |
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REVIEWSRole of SMAD Proteins in Colitis-Associated Cancer: From Known to the Unknown The authors review available evidence linking small mothers against decapentaplegic (SMAD) proteins to colorectal cancer and explore the potential areas for future research in this area. [Oncogene] Abstract Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
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SCIENCE NEWSPhase III BEACON CRC Safety Lead-In Results in BRAF-Mutant Colorectal Cancer Presented Array BioPharma and Pierre Fabre announced safety results and initial clinical activity from the safety lead-in of the Phase III BEACON CRC study evaluating binimetinib, a MEK inhibitor, encorafenib, a BRAF inhibitor and Erbitux®, an anti-EGFR antibody, in patients with BRAF-mutant colorectal cancer (CRC) whose disease has progressed after one or two prior regimens in the metastatic setting. [Press release from Array BioPharma discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release Merck announced the presentation of data from all three cohorts of the registrational, Phase II KEYNOTE-059 trial investigating the use of KEYTRUDA®, the company’s anti-PD-1 therapy, in patients with advanced gastric or gastroesophageal junction adenocarcinoma, including new data in treatment-naïve patients. [Press release from Merck & Co., Inc. discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release | |
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INDUSTRY NEWSLasker Prizes Recognize Work on Cell Growth, Cancer Prevention, and Reproductive Care The Albert and Mary Lasker Foundation announced its three annual prizes, each of which comes with a $250,000 award. Regarded as the United States’s most prestigious biomedical research awards, the Laskers often precede a Nobel Prize in Physiology or Medicine: Eighty-seven Lasker laureates have gone on to win a Nobel. [ScienceInsider] Editorial | Press Release amcure Receives Additional €1.75M BMBF Research Grant amcure announced the approval of a new grant by the German Ministry of Education and Research (BMBF). The grant of approximately €1.75 million covers a portion of the investment needed to advance amcure’s lead candidate, AMC303, which is currently in clinical development. [amcure GmbH] Press Release | |
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POLICY NEWSThe Minister of Science, Kirsty Duncan, announced $515 million in support for fundamental research through the Natural Sciences and Engineering Research Council of Canada’s (NSERC) 2017 competition for the Discovery Grants program, scholarships and fellowships. This is NSERC’s largest annual investment, and it assists researchers by offering financial support though scholarships, fellowships, research supplements, and equipment grants. [Natural Sciences and Engineering Research Council of Canada] Editorial Senate Panel Seeks Middle Ground on Human Fetal Tissue Research and Abortion A Senate spending panel countered a move by its House of Representatives counterpart to quash federal funding for research that uses human fetal tissue from elective abortions. The move sets up a conflict that will need to be resolved when lawmakers meet later this year to hash out differences between the House and Senate bills, which will provide funding for the National Institutes of Health in the 2018 fiscal year. [ScienceInsider] Editorial South Korean Researchers Lobby Government to Lift Human-Embryo Restrictions More than a decade after a fraud scandal in stem-cell science rocked South Korea, scientists in the field are ramping up pressure on the government to relax the country’s strict regulations on human-embryo research — which many researchers label a ban. [Nature News] Editorial Researchers Riled by Lack of Detail in Brexit Science Plans More than one year after UK citizens voted to leave the European Union (EU) and just over two months into ‘Brexit’ negotiations, the British government has finally laid out how it would like to handle scientific relationships with the EU after it leaves the bloc next year. Many scientists are less than impressed. [Nature News] Editorial Senate Spending Panel Approves $2 Billion Raise for NIH in 2018 A Senate subcommittee approved a $2 billion raise, to $36.1 billion, for the National Institutes of Health (NIH) in the 2018 fiscal year. To the relief of research universities, the Senate draft spending bill would also block a Trump proposal to slash NIH payments to cover the overhead costs of research. [ScienceInsider] Editorial
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EVENTSNEW EMBO-EMBL Symposia: Tissue Self-Organization: Challenging the Systems Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Opportunities – Biology of Colorectal Cancer (Albert Einstein College of Medicine) NEW Project Research Scientist – Cancer Genetics (The Francis Crick Institute) NEW Postdoctoral Fellow – Gastric Stem Cells (Harvard University) Research Assistant – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute) Postdoctoral Training Fellow – Systems and Precision Cancer (Institute of Cancer Research) Postdoctoral Research Associate – Intestinal Fibroblast Subsets (University of Oxford) Postdoctoral Position – Epigenetic Dysregulation in Cancer Progression (University of Florida) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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