Intestinal Cell News 5.08 March 8, 2019 | |
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TOP STORYEpithelial Endoplasmic Reticulum Stress Orchestrates a Protective IgA Response Scientists report that intestinal epithelial cell (IEC) endoplasmic reticulum (ER) stress induced a polyreactive immunoglobulin A (IgA) response, which was protective against enteric inflammation. IEC ER stress caused T cell-dependent and -independent and microbiota-independent expansion and activation of peritoneal B1b cells, which culminated in increased lamina propria and luminal IgA. [Science] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)RalA was required within intestinal stem cells (ISCs) for efficient regeneration downstream of Wnt signaling. Within the murine intestine, genetic deletion of either mammalian ortholog, Rala or Ralb, reduced ISC function and Lgr5 positivity, drove hypersensitivity to Wnt inhibition, and impaired tissue regeneration following damage. Ablation of both genes resulted in rapid crypt death. [Cell Stem Cell] Full Article Znhit1 Controls Intestinal Stem Cell Maintenance by Regulating H2A.Z Incorporation The authors showed that deletion of zinc finger HIT-type containing 1 (Znhit1) in the intestinal epithelium depleted Lgr5+ stem cells thus disrupting intestinal homeostasis postnatal establishment and maintenance. [Nat Commun] Full Article Investigators describe and characterize a ‘proteostatic checkpoint’ in Drosophila intestinal somatic stem cells (ISCs). Following a breakdown of proteostasis, ISCs coordinated cell cycle arrest with protein aggregate clearance by Atg8-mediated activation of the Nrf2-like transcription factor cap-n-collar C. [Nat Commun] Full Article Fusobacterium nucleatum Promotes Colorectal Cancer by Inducing Wnt/β-Catenin Modulator Annexin A1 Using an in vitro cancer progression model, researchers discovered that F. nucleatum stimulated the growth of colorectal cancer cells without affecting the pre-cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/β-catenin signaling, was a key component through which F. nucleatum exerted its stimulatory effect. [EMBO Rep] Abstract | Graphical Abstract MEK Nuclear Localization Promotes YAP Stability via Sequestering β-TrCP in KRAS Mutant Cancer Cells In vitro and in vivo results suggest that inhibition of MEK nuclear localization by trametinib synergized with KRAS knockdown or deltarasin treatment in suppressing the viability of KRAS mutant colon cancer cells. [Cell Death Differ] Full Article Cathepsin K (CTSK) contributed to the aggressive phenotype of colorectal cancer (CRC) cells both in vitro and in vivo. Silencing CTSK or administration of Odanacatib, a CTSK-specific inhibitor, totally abolished the CTSK-enhanced migration and motility of CRC cells. [Cell Death Differ] Abstract As neuronal pentraxin 2 (NPTX2) receptors are absent on colorectal carcinoma cells, NPTX2 was shown to physically interact with frizzled class receptor 6 (FZD6) to promote β-catenin translocation into the cell nucleus, resulting in an increase in the expression of MYC, cyclin D1, snail, and N-cadherin along with a decrease in the expression of E-cadherin. [Cell Death Dis] Full Article Entrainment of Superoxide Rhythm by Menadione in HCT116 Colon Cancer Cells Investigators report that the pseudo-steady-state levels of intracellular superoxide (SOX), an important reactive oxygen species, exhibited an inherent rhythm in HCT116 colon cancer cells, which was entrained by the SOX inducer, menadione (MD). This reset was dependent on the expression of p53, and it doubled the sensitivity of the cells to MD. [Sci Rep] Full Article Human colon cancer cells silenced for myoferlin exhibited a reduced oxidative phosphorylation activity associated with mitochondrial fission leading, ROS accumulation, decreased cell growth, and increased apoptosis. [Oncogenesis] Full Article Investigators showed that obesity impaired insulin sensitivity in intestinal epithelial cells (IECs) and that mice with IEC-specific inactivation of the insulin and IGF1 receptors exhibited enhanced colitis-associated cancer development as a consequence of impaired restoration of gut barrier function. [Nat Metab] Abstract Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News. | |
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REVIEWSThe Role of Interleukin-13 in Chronic Inflammatory Intestinal Disorders The authors deal with interleukin-13 (IL-13) in several experimental colitis models -such as oxazolone-, trinitrobenzene sulfonic acid- or dextran sodium sulphate-induced colitis- and chronic intestinal inflammatory disorders -including celiac disease, ulcerative colitis and Crohn’s disease-, and they also highlight the attempts to modulate IL-13 as a therapeutic tool. [Autoimmun Rev] Abstract Induction and Maintenance Treatment of Inflammatory Bowel Disease: A Comprehensive Review Investigators perform a comprehensive review of meta-analysis on comparative of pharmacotherapy used in the management of IBD. [Autoimmun Rev] Abstract Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
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SCIENCE NEWSAbivax Chosen to Deliver ABX464 Oral Presentation Abivax announced that it has been selected after peer-review to deliver an oral presentation on data from ABX464-101, a Phase IIa clinical trial of ABX464 to treat ulcerative colitis as well as 9-month interim data from the ongoing 12-month open-label “maintenance” extension study, ABX464-102. [Press release from Abivax discussing research to be presented at the annual Digestive Disease Week (DDW) Conference, San Diego] Press Release Arena Pharmaceuticals Presented New Phase II Data for Etrasimod and Olorinab Arena Pharmaceuticals, Inc. presented new Phase II data from its investigative drug candidates etrasimod, a next-generation, oral, selective sphingosine 1 phosphate receptor modulator in development for the treatment of moderate to severely active ulcerative colitis, and olorinab, a peripherally restricted, highly selective, full agonist of the cannabinoid receptor type 2 in development for the treatment of visceral pain associated with gastrointestinal diseases. [Press release from Arena Pharmaceuticals, Inc. discussing research presented at the 14th Congress of European Crohn’s and Colitis Organisation (ECCO), Copenhagen] Press Release New data presented show that the subcutaneous formulation of CT-P13 is comparable in terms of efficacy and safety with the intravenous formulation of CT-P13 for the treatment of patients with Crohn’s Disease up to week 54. [Press release from Celltrion Healthcare (Business Wire, Inc.) discussing research presented at the 14th Congress of European Crohn’s and Colitis Organisation (ECCO), Copenhagen] Press Release | |
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INDUSTRY NEWSSTEMCELL Technologies Wins Deloitte Best Managed Companies Award STEMCELL Technologies announced that the company has been selected as a winner of Canada’s Best Managed Companies program for 2019. Canada’s Best Managed Companies is the country’s leading business awards program, recognizing excellence in the management abilities and practices of Canadian owned and managed companies with revenues over $15 million. [STEMCELL Technologies, Inc.] Press Release Synlogic, Inc. announced the advancement of Synthetic Biotic medicines to the lead optimization stage in its collaboration with AbbVie to develop an oral treatment for IBD. [Synlogic, Inc.] Press Release Bexion Pharmaceuticals, Inc. announced Part 3 of their Phase I First-In-Human Trial using BXQ-350 for the treatment of cancer has exceeded expectations in screening and enrollment at their four trial sites. [Bexion Pharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release Evoke Pharma Receives Preliminary FDA Communication on Gimoti™ NDA Evoke Pharma, Inc. announced the receipt of a multi-disciplinary review letter from the FDA in association with the Gimoti 505 New Drug Application. [Evoke Pharma, Inc.] Press Release This award will support Dr. Yoon’s research on establishing a deeper understanding of how gastric cancer stem-like cells lead to distant metastasis and resistance to chemotherapy regimens. [The DeGregorio Family Foundation for Gastric and Esophageal Cancer Research (PR Newswire Association LLC.)] Press Release | |
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POLICY NEWSUK Considers Post-Brexit Research Fund Open to World The UK government is considering creating an international research fund to fill a gap left by the loss of prestigious European Union funding after Brexit. Adrian Smith, director of the Alan Turing Institute in London, will lead a “major” project with the research community to look at establishing such a fund, UK science minister Chris Skidmore told a parliamentary science committee. [Nature News] Editorial Study Finds Gender Imbalances in First-Time NIH Awards Women receiving their first research grant from the National Institutes of Health are awarded an average of $39,000 less than men, according to an analysis published March 5 in JAMA. [The Scientist] Editorial
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EVENTSNEW Keystone Symposia: Integrating Metabolism and Immunity Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESPostdoctoral Fellow – IBD Therapeutics Research (Wellcome Sanger Instiute) PhD Research Fellowship – Pathogenesis of Celiac Disease (University of Oslo) Faculty Position- General Gastroenterology (Oregon Health and Science University) Postdoctoral Research Scientist – Intestinal Stem Cell Biology (Columbia University) Advanced Research Assistant – Inflammatory Bowel Disease Research (Wellcome Sanger Institute) Postdoctoral Position – Colon Cancer (Vanderbilt University) Associate Professor – Oncology (University of California, Davis) Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute) 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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