Intestinal Cell News Volume 5.25 | Jul 12 2019

TOP STORY

Notum Produced by Paneth Cells Attenuates Regeneration of Aged Intestinal Epithelium

Mechanistically, high activity of mammalian target of rapamycin complex 1 in aged Paneth cells inhibited activity of peroxisome proliferator activated receptor α (PPAR-α)3, and lowered PPAR-α activity increased Notum expression. Genetic targeting of Notum or Wnt supplementation restored function of aged intestinal organoids. [Nature] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer

Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant colorectal cancers with immunotherapy. [Cancer Cell] Full Article

Loss of Bcl-G, a Bcl-2 Family Member, Augments the Development of Inflammation-Associated Colorectal Cancer

Researchers showed that from early embryonic development Bcl-G, a Bcl-2 protein family member with unknown function, was highly expressed in gastrointestinal epithelial cells. While Bcl-G was dispensable for normal growth and development in mice, the loss of Bcl-G resulted in accelerated progression of colitis-associated cancer. [Cell Death Differ] Full Article

Anti-Apoptotic Effect by the Suppression of IRF1 as a Downstream of Wnt/β-Catenin Signaling in Colorectal Cancer Cells

Investigators uncovered that the expression of tetratricopeptide repeats 2 was induced by IRF1, which was negatively regulated by the Wnt/β-catenin signaling. In addition, they found that downregulation of IRF1 was mediated by its degradation through the ubiquitination-proteasome pathway, and that decreased activity of a deubiquitinase complex containing USP1 and UAF1 was involved in the degradation of IRF1 by Wnt/β-catenin signaling. [Oncogene] Abstract

Hsa_circ_101555 Functions as a Competing Endogenous RNA of miR-597-5p to Promote Colorectal Cancer Progression

Investigators showed that silencing circ101555 expression significantly suppressed cell proliferation, induced apoptosis and impaired the DNA repair capacity of colorectal cancer (CRC) cells, while rescue experiments suggested that down-expression of miR-597-5p could significantly attenuate the biological effects of circ101555 knockdown on CRC cells. [Oncogene] Abstract

Functional Mismatch Repair and Inactive p53 Drive Sensitization of Colorectal Cancer Cells to Irinotecan via the IAP Antagonist BV6

The authors analyzed the cytostatic/cytotoxic response of colorectal carcinoma cells to irinotecan, depending on the mismatch repair (MMR) and p53 status, and to examine the impact of BV6, a bivalent antagonist of inhibitors of apoptosis c-IAP1/c-IAP2, alone or combined with irinotecan. Therefore, several MSH2- or MSH6-deficient cell lines were complemented for MMR deficiency, or MSH6 was knocked out/down in MMR-proficient cells. [Arch Toxicol] Abstract

Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth

Scientists describe the discovery of the very potent glucose uptake inhibitor Glutor, which targeted glucose transporters GLUT-1, -2, and -3, attenuated glycolytic flux and potently and selectively suppressed growth of a variety of cancer cell lines. Co-treatment of colon cancer cells with Glutor and glutaminase inhibitor CB-839 very potently and synergistically inhibited cancer cell growth. [Cell Chem Biol] Abstract | Graphical Abstract

EZH2 Regulates H2B Phosphorylation and Elevates Colon Cancer Cell Autophagy

Investigators analyzed the association between enhancer of zeste homolog 2 (EZH2) and phosphorylation of H2B at tyrosine 37 (H2B^Y37ph) in colon cancer tissues and cells, along with the influences of the EZH2-H2B^Y37ph axis on colon cancer cell autophagy. Immunohistochemistry was utilized to assess EZH2 and H2B^Y37ph expressions in clinical samples of colon cancer. [J Cell Physiol] Abstract

miR-103/107 Prolong Wnt/β-Catenin Signaling and Colorectal Cancer Stemness by Targeting Axin2

Researchers showed that miR-103/107 stimulated multiple stem-like features in colorectal cancer, including expression of stem-like markers, appearance of side-population cells, and capabilities in self-renewal, tumor initiation, recurrence, and chemoresistance. [Sci Rep] Full Article

Human Intestinal Spheroids Cultured Using Sacrificial Micromolding as a Model System for Studying Drug Transport

The authors report that geometrically controlled self-assembling multicellular intestinal Caco-2 spheroids cultured using sacrificial micromolding displayed reproducible intestinal features and functions that were more representative of the in vivo small intestine than the widely used 2D transwell model. [Sci Rep] Full Article

Single versus Repeated Exposure to Human Polarized Intestinal Epithelial Monolayers for In Vitro Protein Hazard Characterization

Intestinal epithelial cell polarized monolayers were subjected to hazardous or non-hazardous proteins in nine exposures over 30 days and compared to a single exposure of the same protein. The objective was to evaluate whether repeated exposures to a protein differently alter barrier integrity or compromise cell viability compared to single exposures. [Food Chem Toxicol] Full Article

Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News.

Biomarker-Guided Therapy for Colorectal Cancer: Strength in Complexity

Scientists provide an overview of current and emerging clinically relevant biomarkers and their role in the management of patients with colorectal cancer, illustrating the intricacies of biomarker interactions and the growing treatment opportunities created by the availability of comprehensive molecular profiling. [Nat Rev Clin Oncol] Abstract

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

Celsius Therapeutics Signs Collaboration Agreement with Janssen to Identify Response Biomarkers for Ulcerative Colitis

Celsius Therapeutics announced a collaboration with Janssen Biotech, Inc. Under the terms of the agreement, Celsius will apply its proprietary single-cell genomics and machine learning platform to identify predictive biomarkers of response from Janssen’s VEGA study, a Phase IIa clinical trial evaluating the efficacy and safety of combination therapy with guselkumab and golimumab in patients with ulcerative colitis. [Celsius Therapeutics] Press Release

Alfasigma USA Acquires ZELNORM™ (Tegaserod) for Reintroduction to the US Market

Alfasigma USA, Inc. announced it has acquired the brand ZELNORM, a prescription pharmaceutical treatment for irritable bowel syndrome with constipation, from Sloan Pharma S.à r.l., a subsidiary of US WorldMeds Holdings, LLC. [Alfasigma USA, Inc. (Business Wire, Inc.)] Press Release

Cancer Study to Ease Plight at Advanced Stages of Illness

The treatment – called bermekimab – could help with improving outcomes in cancer, including reducing symptoms such as weight loss and decreased mobility. Researchers have been awarded almost £1 million from the Medical Research Council, part of UK Research and Innovation, to enable the study, which will begin recruiting patients later this year. [The University of Edinburgh] Press Release

Learn the basics of culturing mouse intestinal organoids with an instructional video series. Watch the Video Now

University of California Loses Access to New Journal Articles Published by Elsevier after Research Access Fight

Researchers in the University of California system lost subscription access to the major publisher Elsevier, the result of a closely watched fight between the two parties over how academic research should get read and paid for. [STAT News] Editorial

Sweden Passes Law For National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

As Visa Difficulties Persist, Scientists Push for Change

Individual researchers and science societies are finding solutions so colleagues around the globe can attend conferences, from remote presentations to relocating conferences. [The Scientist] Editorial

NEW BIT’s 4^th Annual World Congress of Digestive Disease 2019
November 9-11, 2019
Kunming, China

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

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

NEW Research Technician – Mucosal Immunology (German Research Center for Environmental Health)

NEW Postdoctoral Researcher – Microbiome Interactions in IBD (Quadram Institute Bioscience)

Postdoctoral Fellow – Single Cell Genomics of IBD (Wellcome Sanger Institute)

Postdoctoral Fellowship – Cancer Biology (Ninewells Hospital and Medical School)

Principle Researcher – Systems Disease Biology (Boehringer Ingelheim)

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

Postdoctoral Research – Lipoproteins in IBD (University of Connecticut)

Postdoctoral Fellow – Immunometabolism of IBD (Luxembourg Institute of Health)

Principle Investigator – Gut Physiology (Nestlé Research Center)

Postdoctoral Researcher – Mucosal Immunology and Inflammation (Gilead Sciences, Inc.)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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.