Intestinal Cell News Volume 4.09 | Mar 9 2018

TOP STORY

Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-Like Cells

In patient-derived organoids, primary cells, and cell lines, claudin-2 promoted colorectal cancer self-renewal in vitro and in multiple mouse xenograft models. [Cancer Res] Abstract

(Ranked by impact factor of the journal)

Targeting a Sirt5-Positive Subpopulation Overcomes Multidrug Resistance in Wild-Type Kras Colorectal Carcinomas

Investigators identified a mechanism of multidrug resistance in wild-type Kras colorectal carcinomas (CRCs) based on the survival of a cell subpopulation characterized by Sirt5 expression. Sirt5⁺ cells in wild-type Kras CRCs were resistant to either chemotherapeutic agents or cetuximab and served as a reservoir for recurrence. [Cell Rep] Full Article | Graphical Abstract

Intestinal Epithelial Caspase-8 Signaling Is Essential to Prevent Necroptosis during Salmonella Typhimurium Induced Enteritis

Researchers uncovered that intestinal salmonellosis was associated with strong upregulation of members of the host cell death machinery in intestinal epithelial cells (IECs) as an early event, suggesting that elimination of infected IECs represents a host defense strategy. [Mucosal Immunol] Abstract

A20 Upregulation during Treated HIV Disease Is Associated with Intestinal Epithelial Cell Recovery and Function

Scientists studied intestinal epithelial cells isolated from intestinal biopsies by RNAseq and found that mRNA levels for the ubiquitin-modifying enzyme, A20, are upregulated in antiretroviral therapy-treated individuals and are positively correlated with markers of epithelial function. In a murine intestinal organoid model, A20 expression was suppressed by interferon-alpha (IFNα), which is highly expressed during HIV viremia and induces IFN-mediated signaling. [PLoS Pathog] Full Article

Intracellular Desmoglein-2 Cleavage Sensitizes Epithelial Cells to Apoptosis in Response to Pro-Inflammatory Cytokines

Scientists showed that exposure of intestinal epithelial cells to pro-inflammatory cytokines interferon-gamma and tumor necrosis factor-alpha resulted in Dsg2 intracellular cleavage and generation of a ~55 kDa fragment. [Cell Death Dis] Full Article

Synergistic Actions of FGF2 and Bone Marrow Transplantation Mitigate Radiation-Induced Intestinal Injury

In vitro experiments indicated that FGF2 treatment increased proliferation, reduced apoptosis, and upregulated AKT–GSK3β/β–catenin signaling in irradiated IEC-6 cells. [Cell Death Dis] Full Article

Depletion of Mediator Kinase Module Subunits Represses Super-Enhancer Associated Genes in Colon Cancer Cells

Scientists found that depletion of mediator kinase module subunits MED12, and MED13 with MED13L, can be used to reduce expression of cancer acquired super-enhancer genes such as MYC in colon cancer cells with a concomitant decrease in proliferation. [Mol Cell Biol] Abstract

Zerumbone Reduces Proliferation of HCT116 Colon Cancer Cells by Inhibition of TNF-Alpha

Investigators showed that with the increasing concentration of zerumbone, there was a reduction of HCT116 cells proliferation based on the cell line study and hence higher TNF-alpha inhibition based on the TNF-alpha assay. [Sci Rep] Full Article

Deficiency in DNA Damage Response of Enterocytes Accelerates Intestinal Stem Cell Aging in Drosophila

Scientists showed that deficiency of DNA damage response (DDR) in Drosophila enterocytes (ECs) accelerates intestinal stem cell aging. They generated flies with knockdown of Mre11, Rad50, Nbs1, ATM, ATR, Chk1, and Chk2, which decreased the DDR system in ECs. [Aging (Albany NY)] Full Article

The Coordinated Activities of nAChR and Wnt Signaling Regulate Intestinal Stem Cell Function in Mice

The authors found that coordinated activities of nAChR and Wnt signaling maintain Lgr5-positive stem cell activity and balanced differentiation. [Int J Mol Sci] Full Article

Wnt Signaling in Intestinal Stem Cells: Lessons from Mice and Flies

The authors summarize the latest knowledge acquired from mouse and Drosophila research regarding canonical Wnt signaling and its key functions during stem cell driven intestinal homeostasis, regeneration, aging and cancer. [Genes (Basel)] Full Article

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

Pfizer Announces Favorable Outcome of FDA Advisory Committee Meeting on XELJANZ^® (Tofacitinib) for Moderately to Severely Active Ulcerative Colitis

Pfizer Inc. announced a positive outcome from FDA Gastrointestinal Drugs Advisory Committee (GIDAC) meeting. The GIDAC met to discuss Pfizer’s supplemental New Drug Application for XELJANZ^®, which is currently under review by the FDA, for the treatment of adult patients with moderately to severely active ulcerative colitis. [Pfizer Inc.] Press Release

Bavarian Nordic Announces Phase II Trial Investigating Combination of Its Immunotherapy CV301 and Nivolumab in Microsatellite Stable Colorectal Cancer

Bavarian Nordic A/S announced a new Phase II study, exploring the combination of its cancer vaccine, CV301 and Bristol-Myers Squibb’s nivolumab in patients with metastatic colorectal cancer. CV301 is specifically designed to elicit T-cells against the tumor antigens CEA and MUC1, both of which are highly overexpressed in colorectal cancers. [Bavarian Nordic A/S] Press Release

Seattle Genetics Completes Acquisition of Cascadian Therapeutics

Seattle Genetics, Inc. announced it has completed its previously announced acquisition of Cascadian Therapeutics, Inc. The most advanced program in Cascadian Therapeutics’ pipeline is tucatinib, an investigational oral tyrosine kinase inhibitor that is highly selective for HER2, a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal, ovarian and gastric. [Seattle Genetics, Inc.] Press Release

Meet Dr. Caroline Lindemans and explore her work using organoids to study intestinal repair. Read the Full Profile

Scientists Win and Lose in Texas Primary Contests

Texas primary was the first test for scientists seeking seats in the U.S. House of Representatives, and the results were mixed. [ScienceInsider] Editorial

Behavioral ‘Violations’ Cost Prominent Neuroscientist Positions at Columbia, HHMI

Prominent Columbia University neuroscientist Tom Jessell, 66, has been fired for “serious [behavioral] violations” and the university is closing his lab, the New York City institution said in a statement. The Howard Hughes Medical Institute (HHMI) in Chevy Chase, Maryland, which effectively employed Jessell, a leader in understanding neural development, also terminated him as an investigator because he “violated HHMI policy,” according to a statement from the institute. [ScienceInsider] Editorial

Police Probe of Brazilian Marijuana Researcher Sparks Protests

A police investigation targeting Brazil’s most prominent marijuana researcher has ignited a wave of protest among scientists. They say that the move by authorities from the state of São Paulo threatens research freedoms at a time when science in the country faces severe problems because of draconian budget cuts. [Nature News] Editorial

NEW Gordon Research Conferences: Notch Signaling in Development, Regeneration and Disease
July 22-27, 2018
Lewiston, Maine, United States

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

NEW Postdoctoral Research Fellow – Lysosomes in Neonatal Enterocytes and their Pathologies (Northwestern University)

Director Position – Immune Intestinal Homeostasis (Institute for Basic Science)

Postdoctoral Fellow – Mucosal Immunology (Centre of Molecular Inflammation Research)

Postdoctoral Position – Molecular Biology/Signal Transduction/ Cancer/Inflammation (Universite de Liege)

Academic Positions – Inflammatory Bowel Disease (Cedars-Sinai Inflammatory Bowel and Immunobiology Research Institute)

Clinical Research Training Fellowship – Gastro-Intestinal Pathology with Scientific Research (University College London)

Postdoctoral Research Scientist – Intestinal Biology (Quadram Institute Bioscience)

Postdoctoral Fellow – Inflammatory Bowel Disease (Marshall University)

Postdoctoral Position – Host-Microbe Interactions and Intestinal Cancer (VIB Center for Inflammation Research)

Postdoctoral Fellow – Cancer Biology (Johns Hopkins University)

Postdoctoral Fellow – Cancer Biology (University of Arkansas for Medical Science)

Postdoctoral Position – Intestinal Epithelial Cell Biology and Apical Defense Mechanisms (University of Gothenburg)

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