Intestinal Cell News Volume 5.33 | Sep 6 2019

TOP STORY

Gut-Proglucagon-Derived Peptides Are Essential for Regulating Glucose Homeostasis in Mice

Researchers generated mice with reduction of Gcg expression within the distal or entire gut. Substantial reduction of gut Gcg expression markedly reduced circulating levels of GLP-1, and impaired glucose homeostasis, associated with increased levels of GIP, and accelerated gastric emptying. [Cell Metab] Abstract | Graphical Abstract

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Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection

Infection was significantly increased and minimal bacterial loads were sufficient to invade enterocytes from the apical side and triggered loss of barrier integrity, thereby shifting the paradigm about early stage Shigella invasion. [Cell Host Microbe] Abstract | Graphical Abstract

CD36 Inhibits β-Catenin/c-myc-Mediated Glycolysis through Ubiquitination of GPC4 to Repress Colorectal Tumorigenesis

Scientists discovered that CD36 expression was progressively decreased from adenomas to carcinomas. CD36 loss predicted poor survival of colorectal cancer (CRC) patients. In CRC cells, CD36 acted as a tumor suppressor and inhibited aerobic glycolysis in vitro and in vivo. [Nat Commun] Full Article

A Second Open Reading Frame in Human Enterovirus Determines Viral Replication in Intestinal Epithelial Cells

Investigators characterized an open reading frame (ORF) in human enteroviruses (EVs) that was crucial for viral intestinal infection. Disruption of ORF2p expression decreased the replication capacity of EV-A71 in human intestinal epithelial cells. [Nat Commun] Full Article

Genomically Informed Small-Molecule Drugs Overcome Resistance to a Sustained-Release Formulation of an Engineered Death Receptor Agonist in Patient-Derived Tumor Models

Extrinsic pathway agonists have failed repeatedly in the clinic for three core reasons: inefficient ligand-induced receptor multimerization, poor pharmacokinetic properties, and tumor intrinsic resistance. The authors address these factors by using a highly potent death receptor agonist (DRA), developing an injectable depot for sustained DRA delivery, and leveraging a CRISPR-Cas9 knockout screen in DRA-resistant colorectal cancer cells to identify functional drivers of resistance. [Sci Adv] Full Article

Targeted Mobilization of Lrig1⁺ Gastric Epithelial Stem Cell Populations by a Carcinogenic Helicobacter pylori Type IV Secretion System

Researchers investigated whether microbial effectors with carcinogenic potential influenced Lrig1 progenitor cells ex vivo and via lineage expansion within H. pylori-infected gastric mucosa. [Proc Natl Acad Sci USA] Abstract

Abrogation of EMILIN1-β1 Integrin Interaction Promotes Experimental Colitis and Colon Carcinogenesis

Scientists demonstrated that the expression of the ECM molecule EMILIN-1 halted the development of AOM-DSS induced tumors. In fact, upon AOM-DSS treatment the Emilin1^−/− mice were characterized by a higher tumor incidence, bigger adenomas and less survival. [Matrix Biol] Full Article

KNK437 Restricts the Growth and Metastasis of Colorectal Cancer via Targeting DNAJA1/CDC45 Axis

KNK437 sharply inhibited the level of DnaJ heat shock protein (HSP) family member A1 (DNAJA1), followed by DNAJB1, but had little effect on the levels of HSP27, HSP105, HSP90, and HSP70 in colorectal cancer cells. [Oncogene] Abstract

Metabolic Targeting of HIF-1α Potentiates the Therapeutic Efficacy of Oxaliplatin in Colorectal Cancer

Investigators found that a low-toxicity DNMT inhibitor, zebularine, could downregulate HIF-1α expression and overcome hypoxia-induced oxaliplatin resistance in HCT116 cells and showed efficacy in HCT116 xenograft models and AOM/DSS-induced colorectal cancer mouse models. [Oncogene] Abstract

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The Role of Adaptor Protein CARD9 in Colitis-Associated Cancer

The authors summarize the current understanding of CARD9 functions in colorectal cancer, and discuss its potentially carcinogenic mechanisms. [Mol Ther Oncolytics] Abstract | Full Article

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LONSURF^® (Trifluridine/Tipiracil) Receives Marketing Authorization in Europe for Patients with Previously Treated Metastatic Gastric Cancer

Servier and its partner Taiho Pharmaceutical announced that the European Commission has approved the use of LONSURF^® as monotherapy for the treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction, who have been previously treated with at least two prior systemic treatment regimens for advanced disease. [Servier (Business Wire, Inc.)] Press Release

Turning Point Therapeutics Announces Updated Interim Clinical Data of Repotrectinib and Preclinical Data for TPX-0046, a Novel RET/SRC Inhibitor

Turning Point Therapeutics, Inc. announced updated interim data from the Phase I portion of its ongoing Phase I/II TRIDENT-1 clinical study of lead drug candidate repotrectinib in patients with ROS1-positive non-small cell lung cancer and TRK-positive patients with advanced solid tumors. [Turning Point Therapeutics, Inc.] Press Release

World Health Organization Backs Open-Access Plan S

The World Health Organization is joining cOAlition S, a growing group of agencies and charities that fund scientific research and that require their grantees to share their work in open-access journals or repositories. [The Scientist] Editorial

New Memo Offers First Glimpse of How Trump’s Science Adviser Would Like to Shape Spending Priorities

A new White House directive laying out next year’s spending priorities for federal research agencies describes a US science enterprise imperiled by internal problems and foreign governments. [ScienceInsider] Editorial

NEW Keystone Symposia: Cancer Evolution and Combinatorial Cancer Therapies – Concepts and Challenges
January 19-23, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Researcher – Intestinal Organoids (University of Cambridge)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Intestinal Graft-versus-Host-Disease (Medical College of Wisconsin)

Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit)

Postdoctoral Fellow – Designer Probiotics (Massachusetts General Hospital)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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

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