Intestinal Cell News Volume 5.22 | Jun 21 2019

TOP STORY

IL-33-Mediated Mast Cell Activation Promotes Gastric Cancer through Macrophage Mobilization

Scientists functionally assessed the impact of tumor-adjacent, submucosal mast cell accumulation in murine and human intestinal-type gastric cancer. They found that genetic ablation or therapeutic inactivation of mast cells suppressed accumulation of tumor-associated macrophages, reduced tumor cell proliferation and angiogenesis, and diminished tumor burden. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Tumor Suppressive Autophagy in Intestinal Stem Cells Controls Gut Homeostasis

The authors discovered that deregulated Egfr-Ras85D/Ras1-mitogen-activated protein kinase signaling is the primary trigger for intestinal stem cell proliferation upon disruption of this network and determined that in the mutants, ligand-activated receptors were stabilized and recycled to the cell surface via Rab11-dependent endosomes, rather than being degraded via autophagosomes. [Autophagy] Abstract

Shigella Promotes Major Alteration of Gut Epithelial Physiology and Tissue Invasion by Shutting Off Host Intracellular Transport

Researchers report the multiple effects of two Shigella flexneri effectors, IpaJ and VirA, which targeted small GTPases of the Arf and Rab families, consequently inhibiting several intracellular trafficking pathways. IpaJ and VirA induced large-scale impairment of host protein secretion and block the recycling of surface receptors. [Proc Natl Acad Sci USA] Abstract

DC-SIGN–LEF1/TCF1–miR-185 Feedback Loop Promotes Colorectal Cancer Invasion and Metastasis

Investigators showed that DC-SIGN expression was increased in metastatic colorectal cancer (CRC) cell lines and patient tissues. The overall survival in CRC patients with positive DC-SIGN was remarkably reduced. [Cell Death Differ] Full Article

Expression of UPR Effector Proteins ATF6 and XBP1 Reduce Colorectal Cancer Cell Proliferation and Stemness by Activating PERK Signaling

Researchers generated colorectal cancer cells that harbored doxycycline inducible expression of the active forms of either XBP1(s) or ATF6^1-373. Activation of either XBP1 or ATF6 resulted in reduced cellular proliferation and reduced expression of markers of intestinal epithelial stemness. [Cell Death Dis] Full Article

β-Arrestin1-Mediated Decrease in Endoplasmic Reticulum Stress Impairs Intestinal Stem Cell Proliferation Following Radiation

The authors found that β-arrestin1 (βarr1) knockdown with small interfering RNA significantly enhanced intestinal Lgr5⁺ stem cell proliferation after radiation via directly targeting RNA-like ER kinase. βarr1 offered a promising target for mitigating radiation-induced intestinal injury. [FASEB J] Abstract

Gold Nanoparticles Regulate Tight Junctions and Improve Cetuximab Effect in Colon Cancer Cells

Scientists evaluated cytotoxicity of citrate-capped gold nanoparticles (GNPs) and the role they played on cell–cell adhesion. They also used GNPs for delivery of cetuximab into different colon cancer cell lines. [Nanomedicine (Lond)] Abstract

Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Inhibiting Intestinal Damage via Increasing the Proliferation of Crypt Cells

Ileum toll-like receptor 4 protein expression and nuclear factor kappa-B pathway activation were inhibited. The proliferative ability of enterocytes in the ileum was restored as determined by labeling with proliferation markers. In a three-dimensional culture intestinal crypt organoids study, necrotizing enterocolitis treatment improved the maturation of organoid cells and increased the ratio of proliferative cells under LPS treatment. [Mol Nutr Food Res] Abstract

Environmental Microcystin Targets the Microbiome and Increases the Risk of Intestinal Inflammatory Pathology via NOX2 in Underlying Murine Model of Nonalcoholic Fatty Liver Disease

Both in vivo and in vitro experiments showed that microcystin exposure in NAFLD mice caused rapid alteration of gut microbiome, rise in bacterial genera known for mediating gut inflammation and lactate production. Changes in the microbiome were strongly associated with inflammatory pathology in the intestine, gut leaching, tight junction protein alterations and increased oxidative tyrosyl radicals. [Sci Rep] Full Article

Yeast Screening System Reveals the Inhibitory Mechanism of Cancer Cell Proliferation by Benzyl Isothiocyanate through Down-Regulation of Mis12

Overexpression of the kinetochore protein Mtw1 counteracted the antiproliferative effect of benzyl isothiocyanate (BITC) in yeast. The inhibitory effect of BITC on the proliferation of human colon cancer HCT-116 cells was consistently suppressed by the overexpression of Mis12, a human orthologue of Mtw1, and enhanced by the knockdown of Mis12. [Sci Rep] Full Article

Endoplasmic Reticulum Stress-Mediated Autophagy and Apoptosis Alleviate Dietary Fat-Induced Triglyceride Accumulation in the Intestine and in Isolated Intestinal Epithelial Cells of Yellow Catfish

Investigators used yellow catfish and their isolated intestinal epithelial cells to test the hypothesis that endoplasmic reticulum stress, autophagy, and apoptosis mediate fat-induced changes in lipid metabolism. [J Nutr] Abstract

Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells

Researchers determined the mechanisms involved in the functional transition of Na-K-ATPase during the maturation of crypts to villus cells. Na-K-ATPase activity gradually increased as IEC-18 cells matured in vitro from day zero through day four of post-confluence. [Cells] Full Article

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Mini-Gut: A Promising Model for Drug Development

The authors highlight and discuss the importance of mini-guts for drug development and point out their limitations and future prospects. [Drug Discov Today] Abstract

Gut Organoids: Mini-Tissues in Culture to Study Intestinal Physiology and Disease

Investigators describe the development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer. [Am J Physiol Cell Physiol] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Ironwood and Allergan Report Positive Topline Data from Phase IIIb Trial of LINZESS^® (linaclotide) in Adults with Irritable Bowel Syndrome with Constipation (IBS-C)

Ironwood Pharmaceuticals, Inc. and Allergan plc announced positive topline data from a Phase IIIb clinical trial evaluating LINZESS 290 mcg on multiple abdominal symptoms in adult patients with IBS-C. The trial met its primary multi-component endpoint and demonstrated that linaclotide improved the overall abdominal symptoms of bloating, pain and discomfort in adult IBS-C patients compared to placebo. [Ironwood Pharmaceuticals, Inc.] Press Release

Blueprint Medicines Submits New Drug Application to US Food and Drug Administration for Avapritinib for the Treatment of PDGFRA Exon 18 Mutant GIST and Fourth-Line GIST

Blueprint Medicines Corporation announced it has submitted a New Drug Application to the FDA for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant gastrointestinal stromal tumors (GIST), regardless of prior therapy, and fourth-line GIST. [Blueprint Medicines Corporation] Press Release

Japan Becomes the First Country to Approve Roche’s Personalized Medicine Rozlytrek

Roche announced that Japan’s Ministry of Health, Labour and Welfare has approved Rozlytrek^® for the treatment of adult and pediatric patients with neurotrophic tyrosine receptor kinase fusion-positive, advanced recurrent solid tumors. [Roche] Press Release

Dr. Tamara Zietek discusses the use of intestinal organoids as a model system for nutrient transport. Listen Now

UK’s Leading Mouse Genetics Center Faces Closure

Britain’s leading center for mouse genetics is facing closure in a move that critics say will undermine crucial research on serious diseases and threaten the standing of UK science. The Medical Research Council has told staff at its Harwell Institute in Oxfordshire that an internal strategy board recommended the closure of all academic work at the site, threatening research on diabetes, neurodegenerative disease, child deafness and other conditions. [The Guardian] Editorial

House Panel Clarifies How Universities Would Report Sexual Harassment Cases to US Funders

New rules from the National Science Foundation (NSF) on reporting sexual harassment by someone with an NSF grant raise questions about due process, university administrators say. A key congressional panel took those concerns to heart by modifying language in a bill that would require the administration to write guidelines applying to half a dozen major federal research agencies. [ScienceInsider] Editorial

Academics Join Outcry Sparked by Hong Kong’s Contentious Extradition Bill

Since the bill that would legalize the extradition of people from Hong Kong to mainland China to stand trial or serve criminal sentences was announced, more than a thousand academics from around the world have signed a petition against the proposed law, saying it would restrict free speech and academic debate as well as eroding personal freedoms. [Nature News] Editorial

NEW 14^th World Congress on Inflammation Sydney 2019
September 15-19, 2019
Sydney, Australia

Visit our events page to see a complete list of events in the community.

NEW Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Professor – Microbiomes of the Human Body (The University of South Florida)

Postdoctoral Research – Lipoproteins in IBD (University of Connecticut)

Postdoctoral Fellow – Immunometabolism of IBD (Luxembourg Institute of Health)

Principle Investigator – Gut Physiology (Nestlé Research Center)

Postdoctoral Researcher – Mucosal Immunology and Inflammation (Gilead Sciences, Inc.)

Postdoctoral Fellow – Intestinal and Pulmonary Stem Cell Biology (Stanford School of Medicine)

Postdoctoral Researcher – Intestinal Immunology (KU Leuven)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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