Intestinal Cell News Volume 3.00 | Jan 6 2017

TOP STORY

VGLL4 Targets a TCF4–TEAD4 Complex to Coregulate Wnt and Hippo Signaling in Colorectal Cancer

Researchers report that VGLL4, a previously identified YAP antagonist, functions as a regulator of Wnt/β-catenin signaling. The expression of VGLL4 was significantly downregulated in clinical colorectal carcinoma (CRC) specimens, positively associated with patient survival rate, and inversely correlated with the expression of Wnt target genes in CRCs. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Aquaporin-3 Mediates Hydrogen Peroxide-Dependent Responses to Environmental Stress in Colonic Epithelia

The authors showed that signal transduction by H₂O₂ depends on entry into the cell by transit through aquaporin-3 (AQP3), a plasma membrane H₂O₂-conducting channel. In response to injury, AQP3-depleted colonic epithelial cells showed defective lamellipodia, focal adhesions, and repair after wounding, along with impaired H₂O₂ responses after exposure to the intestinal pathogen Citrobacter rodentium. [Proc Natl Acad Sci USA] Abstract

Sequential HIFU Heating and Nanobubble Encapsulation Provide Efficient Drug Penetration from Stealth and Temperature Sensitive Liposomes in Colon Cancer

The objectives of this study were to: synthesize and characterize long-circulating echogenic nanobubble encapsulated low temperature sensitive liposomes and encapsulated non-thermosensitive liposomes, evaluate in vivo drug release following short duration high intensity focused ultrasound (HIFU) treatments administered sequentially over an hour in a large volume of mouse xenograft colon tumor, and determine the impact of the HIFU/nanobubble combination on intratumoral drug distribution. [J Control Release] Abstract

Colorectal Mixed Adenoneuroendocrine Carcinomas and Neuroendocrine Carcinomas Are Genetically Closely Related to Colorectal Adenocarcinomas

Tissue from 19 colorectal mixed adenoneuroendocrine carcinomas and eight colorectal poorly differentiated neuroendocrine neoplasms (neuroendocrine carcinomas) was microdissected and subjected to next-generation sequencing using a colorectal adenocarcinoma-specific panel comprising 196 amplicons covering 32 genes linked to colorectal adenocarcinoma, and poorly differentiated neuroendocrine neoplasm tumorigenesis. [Mod Pathol] Abstract

Identification of Genetic Susceptibility Loci for Intestinal Behçet’s Disease

Researchers aimed to identify distinctive genetic susceptibility loci/genes associated with intestinal involvement in Behçet’s disease and determine their roles in intestinal inflammation as well as their interactions with genes involved in inflammatory bowel disease. [Sci Rep] Full Article

Genetic Disruption of the pH_i-Regulating Proteins Na⁺/H⁺ Exchanger 1 (SLC9A1) and Carbonic Anhydrase 9 Severely Reduces Growth of Colon Cancer Cells

The authors investigated the role of carbonic anhydrase 9 (CA9) via complete genomic knockout (ko) and compared its impact on tumor cell physiology with the essential _i regulator Na⁺/H⁺ exchanger 1 (NHE1). Initially, they established NHE1-ko LS174 cells with inducible CA9 knockdown. [Oncotarget] Full Article

HuR Enhances Early Restitution of the Intestinal Epithelium by Increasing Cdc42 Translation

Scientists showed that HuR is essential for early intestinal epithelial restitution by increasing the expression of cell division control protein 42 (Cdc42) at the posttranscriptional level. HuR bound to the Cdc42 mRNA via its 3′-untranslated region and this association specifically enhanced Cdc42 translation without effect on Cdc42 mRNA level. [Mol Cell Biol] Abstract

Crosstalk between Alternatively Spliced UGT1A Isoforms and Colon Cancer Cell Metabolism

Investigators hypothesized that glucuronosyltransferase 1 gene locus (UGT1) A_i2s function into a complex protein network connecting other metabolic pathways with influence on cancer cell metabolism. This is based on a pathway enrichment analysis of proteomic data that identified several high-confidence candidate interaction proteins of UGT1A_i2 proteins in human tissues, namely the rate-limiting enzyme of glycolysis pyruvate kinase, which plays a critical role in cancer cell metabolism and tumor growth. [Mol Pharmacol] Abstract | Full Article

Postnatal Human Enteric Neuronal Progenitors Can Migrate, Differentiate, and Proliferate in Embryonic and Postnatal Aganglionic Gut Environments

Enteric neural stem/progenitor cells (ENSCs) were isolated from the intestines of 25 patients undergoing bowel resection, including 7 children with Hirschsprung disease (HSCR). Neuronal differentiation and proliferation of ENSCs from submucosal and myenteric plexuses from patients with and without HSCR were characterized. [Pediatr Res] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

ANGPTL2 Expression in the Intestinal Stem Cell Niche Controls Epithelial Regeneration and Homeostasis

Scientists assessed angiopoietin-like protein 2 (ANGPTL2) function in intestinal physiology and disease in vivo. Although intestinal development proceeded normally in Angptl2-deficient mice, expression levels of the intestinal stem cell marker gene Lgr5 decreased, which was associated with decreased transcriptional activity of β-catenin in Angptl2-deficient mice. [EMBO J] Full Article

Functional Transcriptomics in Diverse Intestinal Epithelial Cell Types Reveals Robust microRNA Sensitivity in Intestinal Stem Cells to Microbial Status

Researchers provide novel evidence that microbiota may control intestinal epithelial stem cell proliferation in part through microRNAs (miRNAs). They demonstrated that miRNA profiles differ dramatically across functionally distinct cell types of the mouse jejunal intestinal epithelium and that miRNAs respond to microbiota in a highly cell-type specific manner. [J Biol Chem] Abstract | Full Article

Collateral Damage: Insights into Bacterial Mechanisms that Predispose Host Cells to Cancer

The authors discuss how bacterial pathogens interact with host cells to contribute to the development of cancer. [Nat Rev Microbiol] Abstract

Meta-Analytic Bayesian Model For Differentiating Intestinal Tuberculosis from Crohn’s Disease

Distinguishing intestinal tuberculosis (ITB) from Crohn’s disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory findings that help to differentiate these two diseases. The authors aimed to produce estimates of the predictive power of these findings and construct a comprehensive model to predict the probability of ITB vs. CD. [Am J Gastroenterol] Abstract

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

Enterome Starts Phase I Clinical Trial with Its Lead Candidate EB8018 to Treat Crohn’s Disease

Enterome SA announced the launch of a Phase I clinical study with its lead small molecule drug candidate EB8018, a small molecule designed to block FimH, as a potential new treatment for Crohn’s disease. [Enterome SA] Press Release

Rebiotix Treats First Patient in Phase I Study of RBX7455, an Orally Delivered Broad-Spectrum Non-Frozen Microbiota Capsule for Recurrent Clostridium difficile Infection

Rebiotix Inc. announced that the first patient has been treated in a Phase I study of RBX7455 for the prevention of recurrent C. difficile infection. [Rebiotix Inc.] Press Release

Takeda and PvP Biologics Announce Development Agreement Around Novel Therapeutic for Celiac Disease

Takeda Pharmaceutical Company Limited and PvP Biologics, Inc. announced a global agreement for the development of KumaMax, a novel enzyme designed to break down the immune-reactive parts of gluten in the stomach, thereby avoiding the painful symptoms and damage done in the small intestine from accidental gluten ingestion. [Takeda Pharmaceutical Company Limited] Press Release

US Scientists Fear New Restrictions on Fetal-Tissue Research

House Republicans conclude that tissue from aborted fetuses is of limited value for research and seek to reduce funding. [Nature News] Editorial

Argentina’s Researchers Occupy Science Ministry

Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. [Nature News] Editorial

NEW Keystone Symposium: Tumor Metabolism: Mechanisms and Targets
March 5-9, 2017
Whistler, Canada

NEW Intestinal Organoid In-Person Training
May 9-10, 2017
Vancouver, Canada

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

NEW Research Fellow – Cross Talk between Immune Cells, Microbes and the Intestinal Barrier (University of Michigan Ann Arbor)

NEW Project Scientist – Early Life Microbiota Interaction with the Host (Institute of Food Research)

Research Associate – Epigenetics of Human Intestinal Epithelial Cell Pathophysiology (University of Cambridge)

Assistant Professor – Gastrointestinal Health/Physiology Tenure-Track Faculty Position (University of Maryland)

Scientific Writing Associate – Literature Review/Analysis and Relevant Scientific and Medical Material (Genfit SA)

Tenure-Track Position – Various Projects (University Medical Center Utrecht)

Research Officer – Transcriptional and Epigenetic Regulation in Colon Cancer and Intestinal Development (Hudson Institute of Medical Research)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Assistant or Associate Member – Stem Cell/Gene Therapy (Fred Hutchinson Cancer Research Center)

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