Intestinal Cell News Volume 3.03 | Jan 27 2017

TOP STORY

Epithelial Expression and Function of Trypsin-3 in Irritable Bowel Syndrome

Researchers showed in irritable bowel syndrome, the intestinal epithelium produces and releases the active protease trypsin-3, which is able to signal to enteric neurons and to induce visceral hypersensitivity. [Gut] Full Article

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Pleckstrin Homology Domain-Containing Protein PHLDB3 Supports Cancer Growth via a Negative Feedback Loop Involving p53

Scientists identified a pleckstrin homology domain-containing protein (PHLDB3)-encoding gene as a p53 target. PHLDB3 overexpression increases proliferation and restrains apoptosis of wild-type p53-harboring cancer cells by reducing p53 protein levels. [Nat Commun] Full Article

DNA Copy Number Changes Define Spatial Patterns of Heterogeneity in Colorectal Cancer

Investigators examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumors and matched metastases from 27 patients, they observed inter-tumor concordance for coding mutations; in contrast, gene copy numbers are highly discordant between primary tumors and metastases as validated by fluorescent in situ hybridization. [Nat Commun] Full Article

Centrosome Amplification Is Sufficient to Promote Spontaneous Tumorigenesis in Mammals

Scientists tested the consequence of centrosome amplification by creating mice in which centrosome number can be chronically increased in the absence of additional genetic defects. They showed that increasing centrosome number elevated tumor initiation in a mouse model of intestinal neoplasia. [Dev Cell] Abstract | Graphical Abstract

The miR-487b-3p/GRM3/TGFβ Signaling Axis Is an Important Regulator of Colon Cancer Tumorigenesis

Researchers demonstrated that expression of GRM3, a metabotropic glutamate receptor mainly expressed in mammalian central nervous system, was significantly upregulated in majority of human colonic adenocarcinomas tested and colon cancer cell lines. [Oncogene] Abstract

Cortactin Deficiency Causes Increased RhoA/ROCK1-Dependent Actomyosin Contractility, Intestinal Epithelial Barrier Dysfunction, and Disproportionately Severe DSS-Induced Colitis

Given that cortactin controls endothelial permeability, scientists hypothesized that cortactin is also important for epithelial barrier regulation. In healthy human colon tissues, cortactin co-localized with ZO-1 at epithelial cell contacts. In inflammatory bowel diseases patients, they observed decreased cortactin levels and loss of co-localization with ZO-1. [Mucosal Immunol] Abstract

The Depletion of ATM Inhibits Colon Cancer Proliferation and Migration via B56γ2-Mediated Chk1/p53/CD44 Cascades

Ataxia-telangiectasia mutated (ATM) protein kinase is a major guardian of genomic stability, and its well-established function in cancer is tumor suppression. Researchers reported an oncogenic role of ATM. Using two isogenic sets of human colon cancer cell lines that differed only in their ATM status, they demonstrated that ATM deficiency significantly inhibits cancer cell proliferation, migration, and invasion. [Cancer Lett] Abstract

Droplet-Based Microtumor Model to Assess Cell-ECM Interactions and Drug Resistance of Gastric Cancer Cells

Since extracellular matrix influences the biological behavior of tumor cells, scientists hypothesized that gastric cancer might be more similarly modeled in three-dimensional (3D) with matrix rather than in 2D. Herein, they developed a microfluidic-based a 3D in vitro gastric cancer model, with subsequent drug resistance assay. [Sci Rep] Full Article

Identification of Downstream Metastasis-Associated Target Genes Regulated by LSD1 in Colon Cancer Cells

The authors aimed to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. [Oncotarget] Full Article

Calreticulin Is a Fine Tuning Molecule in Epibrassinolide-Induced Apoptosis through Activating Endoplasmic Reticulum Stress in Colon Cancer Cells

Investigators revealed that epibrassinolide treatment caused endoplasmic reticulum stress and UPR by altering calreticulin expression causing caspase-dependent apoptosis in HCT 116, HT29, DLD-1 and SW480 colon cancer cells. [Mol Carcinog] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Genome Engineering of Stem Cell Organoids for Disease Modeling

The authors summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling. [Protein Cell] Full Article

The Heterocellular Emergence of Colorectal Cancer

Using colorectal cancer as an example, the author reviews how heterotypic cells differentially communicate to support emergent malignancy. [Trends Cancer] Full Article

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

National Institutes of Health Honors Research Leaders from University Hospitals and Case Western Reserve University with Prestigious Outstanding Investigator Awards

Two internationally recognized medical research leaders from University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine have received Outstanding Investigator Awards from the National Institutes of Health (NIH). The 7-year, $6.7 million dollar awards, which are the highest honor and largest individual support grants conferred by the NIH, will advance promising molecular studies of colon cancer and age-related cardiovascular risks, respectively. [University Hospitals, Cleveland] Press Release

OncoMed Initiates Enrollment of Phase Ib Clinical Trial of Brontictuzumab for the Treatment of Metastatic Colorectal Cancer Patients

OncoMed Pharmaceuticals, Inc. announced dosing of the first patient in a Phase Ib clinical trial of brontictuzumab plus chemotherapy in patients with metastatic colorectal cancer. [OncoMed Pharmaceuticals, Inc.] Press Release

Proposed U.S. Biotech Rules Raise Industry Hopes and Anxieties

Makers of genetically engineered products have long been on the lookout for changes in U.S. regulations. The system that divvies up the safety review of these products between the Food and Drug Administration, Environmental Protection Agency, and U.S. Department of Agriculture is in the middle of a years-long overhaul, in part to accommodate modern gene-editing technologies such as CRISPR. And a set of new proposals released last week offers hints about what those agencies still hope to change. [ScienceInsider] Editorial

World’s Foremost Institute on Death and Disease Metrics Gets Massive Cash Boost

The world’s premier center for health metrics — the science of measuring and analyzing global health problems, and how they relate to healthcare and biomedical research funding — will receive a US$279-million cash injection from the Bill & Melinda Gates Foundation. The cash will go towards expanding the institute’s work over the next decade and consolidating its primacy in the field. It is considered by far the biggest and most influential research center for health metrics, and its work informs the funding and policy decisions of many national governments and local, regional and global organizations, including the World Bank and the US National Institutes of Health. [Nature News] Editorial

Trump Agenda Threatens US Legacy of Science Diplomacy

A newly minted leader with no experience governing at home or establishing policy abroad now oversees the United States’ vast diplomatic enterprise. US President Donald Trump has a deep bench of scientific and technical expertise to tap across multiple government agencies — but it is not clear that he will use it. [Nature News] Editorial

Candidates from Ethiopia, United Kingdom, and Pakistan Will Compete for WHO’s Top Slot

The World Health Organization (WHO) announced who will be up for election to the post of director-general in May. They are: former Ethiopian health minister and minister of foreign affairs Tedros Adhanom Ghebreyesus; British physician and United Nations official David Nabarro; and Pakistani cardiologist and former science minister Sania Nishtar. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Cilia, Mucus & Mucociliary Interactions
February 12-17, 2017
Galveston, Texas, United States

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

NEW Postdoctoral Researcher – Organoid Technology (Hubrecht Organoid Technology)

NEW Research Associate – Colorectal Cancer (University of Virginia)

NEW Postdoctoral Research Scientist – Epithelial Homeostasis and Cancer (Medical Research Council)

NEW Gastroenterologist(s) – General and Interventional (Temple University)

NEW Postdoctoral Fellow – Translational Intestinal Models (Johnson & Johnson Group)

NEW Postdoctoral Fellowship – Neuro-Immune Regulation of Mucosal Barrier Function (Linköping University)

Postdoctoral Research Fellow – Intestinal Disease (Children’s Hospital Los Angeles)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Intestinal Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.