Intestinal Cell News Volume 6.04 | Feb 7 2020

TOP STORY

Methylglyoxal Scavengers Resensitize KRAS-Mutated Colorectal Tumors to Cetuximab

Mutant KRAS cells under methylglyoxal (MGO) stress showed AKT-dependent survival when compared with wild-type KRAS isogenic colorectal cancer cells. MGO induced AKT activation through phosphatidylinositol 3-kinase/mammalian target of rapamycin 2 and Hsp27 regulation. [Cell Rep] Full Article | Graphical Abstract

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Cohesin Controls Intestinal Stem Cell Identity by Maintaining Association of Escargot with Target Promoters

Scientists showed that the Cohesin complex prevented premature differentiation of Drosophila intestinal stem cells (ISCs) into enterocytes (ECs). Depletion of the Cohesin subunit Rad21 and the loading factor Nipped-B triggered an ISC to EC differentiation program that was independent of Notch signaling, but could be rescued by over-expression of the ISC-specific escargot transcription factor. [eLife] Full Article

Selective Deletion of MyD88 Signaling in α-SMA Positive Cells Ameliorates Experimental Intestinal Fibrosis via Post-Transcriptional Regulation

Human intestinal myofibroblasts were exposed to various bacterial components and assessed for fibronectin and collagen I production. [Mucosal Immunol] Abstract

Ferroptosis Involves in Intestinal Epithelial Cell Death in Ulcerative Colitis

Investigators showed that ferroptosis was significantly induced in intestinal epithelial cells from ulcerative colitis patients and mice with colitis, and the ferroptosis was mediated by endoplasmic reticulum stress signaling. [Cell Death Dis] Full Article

Comprehensive Analysis of RNA Sequencing in Adenoma-Cancer Transition Identified Predictive Biomarkers and Therapeutic Targets of Human Colorectal Cancer

Researchers carried out high-throughput RNA sequencing to determine the expression profiles of circRNAs, miRNAs and mRNAs in human colorectal cancer, adenoma and adjacent normal tissues. [Mol Ther Nucleic Acids] Abstract

Butyrate Inhibits Deoxycholic‐Acid‐Resistant Colonic Cell Proliferation via Cell Cycle Arrest and Apoptosis: A Potential Pathway Linking Dietary Fiber to Cancer Prevention

With human HCT‐116 cells as parental colonic cells, a human deoxycholic acid (DCA)‐resistant colonic cell line (DCA‐RCL) was developed. DCA treatment increased apoptosis and intracellular reactive oxygen species at a rate 3‐ fold greater in HCT‐116 cells than in DCA‐RCL cells. [Mol Nutr Food Res] Abstract

Preferential Uptake of Polyunsaturated Fatty Acids by Colorectal Cancer Cells

To explain the mechanism of polyunsaturated fatty acid (PUFA) alterations in colorectal cancer, the authors measured fatty acid uptake by colon cancer cells and normal colon cells. The levels of PUFAs in colon cancer cell culture medium decreased significantly with incubation time, while no changes were observed in the medium in which normal colon cells were incubated. [Sci Rep] Full Article

Minecoside Modulates Cell Invasion via Regulation of CXCR4 Expression in Breast and Colon Cancer Cells

Minecoside-mediated suppression of CXC chemokine receptor 4 expression inhibited CXC ligand 12-induced invasion of breast and colorectal cancer cells. [Planta Med] Abstract

CD74 Signaling Links Inflammation to Intestinal Epithelial Cell Regeneration and Promotes Mucosal Healing

The authors studied the characteristics of CD74 protein expression in human inflammatory bowel disease, and experimental colitis. The functional role of CD74 signaling in the intestine was investigated using cellular models, wild type, CD74^-/-, and BM chimera mice, neutralizing anti-CD74 antibodies, flow cytometry, immunohistochemistry, immunofluorescence, immunoblotting and CRISPR-Cas technology. [Cell Mol Gastroenterol Hepatol] Abstract

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Roles of nAChR and Wnt Signaling in Intestinal Stem Cell Function and Inflammation

In the intestine, the Wnt signaling pathway plays a central role in the epithelium and is a principal regulator of intestinal stem cell (ISC) identity and proliferation. Since Wnt signaling was first described more than 40 years ago in ISCs, large amounts of scientific evidence have demonstrated remarkable long-term self-renewal capacity of ISCs. [Int Immunopharmacol] Abstract

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Blueprint Medicines Announces PDUFA Date Extension for New Drug Application of Avapritinib for the Treatment of Adults with Fourth-Line Gastrointestinal Stromal Tumor

Blueprint Medicines Corporation announced that the FDA has extended the Prescription Drug User Fee Act (PDUFA) date for its New Drug Application seeking accelerated approval of avapritinib for the treatment of adults with fourth-line gastrointestinal stromal tumor. [Blueprint Medicines Corporation] Press Release

Onvasertib Demonstrates Effectiveness as Pan-KRAS Inhibitor with Confirmed Tumor Regression and Clinical Benefit Achieved in KRAS-Mutated mCRC Patients

Trovagene, Inc. announced positive data from an ongoing Phase Ib/II clinical trial of onvansertib plus FOLFIRI and Avastin^® for second-line treatment of KRAS-mutated metastatic colorectal cancer (mCRC). [Trovagene, Inc.] Press Release

Ex-Emory Scientist with Ties to China Charged with Fraud

A former Emory University neuroscientist has been charged with defrauding the US government by taking a salary from a Chinese institution while also being paid through research grants from the National Institutes of Health. The charges against Li Xiao-Jiang were filed on 21 November 2019 in US district court in Atlanta and were first reported by NBC News. [ScienceInsider] Editorial

Chan Zuckerberg Initiative to Fund 30 Patient Groups, Aiming to Build a Model for Tackling Rare Diseases

On January 3^rd, Mark Zuckerberg and his spouse Dr. Priscilla Chan’s philanthropic vehicle announced a set of grants that executives there hope will create a model for tackling any rare disease: financing patient-led groups, and giving them training and resources. [STAT News] Editorial

NEW Pluripotent Stem Cell Training
April 22-24, 2020
Vancouver, British Columbia, Canada

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NEW Postdoctoral Position – Intestinal Immunity (The University of Chicago)

Postdoctoral Associate – Intestinal Immunology (The Scripps Research Institute)

PhD Student – Biology of Stem Cells (Dresden University of Technology)

Postdoctoral Position – Epigenetic Control by the Novel Histone Methyltransferase KMT9 (University of Freiburg)

Research Scientist – Inflammatory and Autoimmune Disorders (Genentech, Inc.)

Senior Scientist – Drug Concept Discovery (Boehringer Ingelheim)

Faculty Scientist Position – IBD Research (The University of Texas Health Science Center at Houston)

Postdoctoral Research Fellow – Tumor Microenvironment (Fred Hutchinson Cancer Research Center)

Research Scientist – In Vivo Research on Wnt Signaling in Self-Renewel (Surrozen)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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