Intestinal Cell News Volume 3.24 | Jun 30 2017

TOP STORY

Rare Cells Are ‘Window into the Gut’ for the Nervous System

Specialized cells in the gut sense potentially noxious chemicals and trigger electrical impulses in nearby nerve fibers. Using gut-mimicking “organoids” grown from mouse stem cells, researchers showed how cells in the intestinal lining called enterochromaffin cells alert the nervous system to signs of trouble in the gut, from bacterial products to inflammatory food molecules. [Press release from the University of California, San Francisco discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Interaction of Tankyrase and Peroxiredoxin II Is Indispensable for the Survival of Colorectal Cancer Cells

The authors demonstrated that peroxiredoxin type II (PrxII) plays a tumor-promoting role in colorectal cancer by interacting with a poly(ADP-ribose) polymerase tankyrase. PrxII deletion in mice with inactivating mutation of adenomatous polyposis coli gene reduced intestinal adenomatous polyposis via Axin/β-catenin axis and thereby promoted survival. [Nat Commun] Full Article

Hypoxia-Induced Downregulation of DUSP-2 Phosphatase Drives Colon Cancer Stemness

Scientists report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP-2) is critical for the accumulation of cancer stem-like cells in colorectal cancer. Reduced expression of DUSP-2 led to overproduction of cyclooxygenase-2-derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways. [Cancer Res] Abstract

NOD2 Suppresses Colorectal Tumorigenesis via Downregulation of the TLR Pathways

Investigators showed that Nod2-deficient mice are highly susceptible to experimental colorectal tumorigenesis independent of gut microbial dysbiosis. The expression of inflammatory genes and the activation of inflammatory pathways, including NF-κB, ERK, and STAT3 were significantly higher in Nod2^−/− mouse colons during colitis and colorectal tumorigenesis, but not at homeostasis. [Cell Rep] Full Article | Graphical Abstract

Downregulated USP3 mRNA Functions as a Competitive Endogenous RNA of SMAD4 by Sponging miR-224 and Promotes Metastasis in Colorectal Cancer

The authors found that USP3 modulated SMAD4 expression in a miRNA dependent, and protein-coding gene independent manner. USP3 and SMAD4 were directly targeted by miR-224, and overexpression of the USP3 3′UTR could inhibit metastasis caused by the loss of USP3. [Sci Rep] Full Article

Synergistic Inhibition of Colon Cancer Growth by the Combination of Methylglyoxal and Silencing of Glyoxalase I Mediated by the STAT1 Pathway

Methylglyoxal (MG) and glyoxalase I (GLOI) levels were manipulated in colon cancer cells and the effects on their viability, proliferation, apoptosis, migration, and invasion in vitro were quantified by Cell Counting Kit-8, colony formation assay, flow cytometry, and transwell assays. The antitumor effects of MG and silencing of GLOI were investigated in vivo in a SW620 colon cancer xenograft model in BALB/c nude mice. [Oncotarget] Full Article

G Protein-Coupled Receptor 35 Contributes to Mucosal Repair in Mice via Migration of Colonic Epithelial Cells

Researchers investigated the contribution of G protein-coupled receptor 35 (GPR35)-mediated signaling to mucosal repair of colonic epithelium in IBD. GPR35 function was examined in a wound healing model, using young adult mouse colon epithelium cells, and in a dextran sulphate sodium-induced mouse model of colitis. [Pharmacol Res] Abstract | Graphical Abstract

G-Protein-Coupled Receptor Kinase-2 Is a Critical Regulator of TNFα Signaling in Colon Epithelial Cells

Scientists examined the role of G-protein-coupled receptor kinase-2 (GRK2) in TNFα signaling in colon epithelial cell–biological processes including wound healing, proliferation, apoptosis, and gene expression. Knockdown of GRK2 in the SW480 human colonic cells significantly enhanced TNFα-induced epithelial cell wound healing without any effect on apoptosis/proliferation. [Biochem J] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

MicroRNA-122a Regulates Zonulin by Targeting EGFR in Intestinal Epithelial Dysfunction

The authors aimed to investigate the role of miR-122a in regulating zonulin during the modulation of intestinal barrier. Zonulin proteins and their target gene expression were analyzed in miR-122a-overexpressing cell lines and in the target gene of epidermal growth factor receptor (EGFR). [Cell Physiol Biochem] Full Article

Kaiso Differentially Regulates Components of the Notch Signaling Pathway in Intestinal Cells

Investigators demonstrated that Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation. Moreover, Kaiso regulated several components of the Notch signaling pathway in intestinal cells, namely, Dll-1, Jagged-1 and Notch1. [Cell Commun Signal] Full Article

Butyrate Modifies Intestinal Barrier Function in IPEC-J2 Cells through a Selective Upregulation of Tight Junction Proteins and Activation of the Akt Signaling Pathway

Researchers investigated the effect of butyrate on intestinal epithelial integrity and tight junction permeability in a model of LPS-induced inflammation in IPEC-J2 cells. Butyrate dose-dependently reduced LPS impairment of intestinal barrier integrity and tight junction permeability, measured by trans-epithelial electrical resistance and paracellular uptake of fluorescein isothiocyanate-dextran. [PLoS One] Full Article

Intestinal Lymphatic Vasculature: Structure, Mechanisms and Functions

The authors provide in-depth information concerning the organization and structure of intestinal lymphatics, the current view of their developmental origins, as well as molecular mechanisms of intestinal lymphatic patterning and maintenance. [Nat Rev Gastroenterol Hepatol] Abstract

Bioengineering for Intestinal Organoid Cultures

Scientists cover recent bioengineering approaches to improve organoid maturation, scale up, reproducibility and analysis. [Curr Opin Biotechnol] Abstract | Graphical Abstract

Signaling and Epigenetic Mechanisms of Intestinal Stem Cells and Progenitors: Insight into Crypt Homeostasis, Plasticity, and Niches

Highlighting recent studies investigating signaling, transcriptional, and epigenetic mechanisms of intestinal epithelial cells, researchers discuss the mechanisms underlying crypt homeostasis, plasticity, and niches. [Wiley Interdiscip Rev Dev Biol] Abstract

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

Boston Biomedical Presents Data for Investigational Cancer Stemness Inhibitor Napabucasin in Metastatic Colorectal and Pancreatic Cancer

Boston Biomedical, Inc. featured two oral and two poster presentations evaluating napabucasin in metastatic colorectal cancer and pancreatic adenocarcinoma. [Press release from Boston Biomedical, Inc. discussing research presented at the 2017 European Society of Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer, Barcelona] Press Release

Volition to Present at the EuropaColon Advocacy Masterclass and Exhibit

VolitionRx Limited announced it will be presenting at the EuropaColon Advocacy Masterclass. [Press release from VolitionRx Limited discussing research to be presented at the 2017 European Society of Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer, Barcelona] Press Release

Organoids Proposed to Screen Patients for High-Priced Drugs

Medical scientist Hans Clevers thinks tests in lab-grown mini-organs could help make expensive drugs more cost-effective by identifying patients who are and aren’t likely to benefit. [MIT Technology Review] Press Release

FDA Approves Vectibix^® (Panitumumab) for Use in Wild-Type RAS Metastatic Colorectal Cancer

Amgen announced that the FDA has approved the supplemental Biologics License Application for Vectibix^® for patients with wild-type RAS metastatic colorectal cancer as first-line therapy in combination with FOLFOX and as monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. [Amgen Inc.] Press Release

Synthetic Biologics Announces Allowance of Key U.S. Patent Covering SYN-010 Intended for the Novel Treatment of Irritable Bowel Syndrome with Constipation (IBS-C)

Synthetic Biologics, Inc. announced that the U.S. Patent and Trademark Office issued a Notice of Allowance for a patent application which covers the use of the active agent of SYN-010, the company’s proprietary, modified-release formulation of lovastatin lactone, for the treatment of constipation. [Synthetic Biologics, Inc.] Press Release

Illumina Announces FDA-Approved Next-Generation Sequencing Cancer Companion Diagnostic Test Kit

Illumina, Inc. announced its Extended RAS Panel, an FDA-approved next-generation sequencing kit that meets the newly published guidelines for evaluation of colorectal cancer from the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. [Illumina, Inc.] Press Release

Canada’s Basic Science at Risk of Fading Away, Report Argues

Canada’s scientific enterprise is at risk of sinking to junk bond status as a result of a funding crunch and misguided government and granting council policies, argues a report. In particular, the authors decry a steady shift away from basic science that has left a smaller portion of the nation’s growing scientific community focused on fundamental research. [ScienceInsider] Editorial

Putin Tightens Control over Russian Academy of Sciences

The Russian government has taken further steps to tighten its grip on the Russian Academy of Sciences (RAS) in Moscow. The State Duma—one of the two chambers of the Russian parliament—passed the first draft of a new law that would give president Vladimir Putin the final say in the elections for RAS’s presidency. [ScienceInsider] Editorial

Scientists in Limbo as US Supreme Court Allows Modified Travel Ban

The US Supreme Court has reinstated a limited version of President Donald Trump’s temporary order banning travelers from six Muslim-majority countries from entering the United States. The court will hear a legal challenge to the ban in October. The court’s decision casts doubt on the fate of students and scientists from these countries who hope to study or work in the United States. [Nature News] Editorial

NEW Cold Spring Harbor Stem Cell Biology Meeting
September 25-27, 2017
Cold Spring Harbor, New York, United States

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

NEW Postdoctoral Position – Intestinal Epithelial Cell Biology (University of Gothenburg)

NEW Postdoctoral Fellowships – Epithelial Cell Biology & Gastrointestinal Neoplasia (Vanderbilt University)

Postdoctoral Research Associate – Colorectal Cancer (University of Virginia)

Postdoctoral Position – Cancer Genomics and Precision Medicine (Candiolo Cancer Institute-FPO, IRCCS)

Postdoctoral Fellow – Intestinal Pathogen Research (Boston Children’s Hospital and Harvard Medical School)

Postdoctoral Researcher – Colorectal Cancer (NUI Galway)

PhD Studentship – Human Intestinal Epithelial Cell Biology (University of Cambridge)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

Postdoctoral Research Fellow – Cancer Epidemiology (Fred Hutchinson Cancer Research Center)

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

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