Intestinal Cell News Volume 4.48 | Dec 14 2018

TOP STORY

Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance

Scientists showed that the expression of atypical protein kinase C ζ (PKCζ) and PKCλ/ι was reduced in human serrated tumors. Simultaneous inactivation of the encoding genes in the mouse intestinal epithelium resulted in spontaneous serrated tumorigenesis that progressed to advanced cancer with a strongly reactive and immunosuppressive stroma. [Immunity] Abstract | Press Release | Graphical Abstract

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Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development

Investigators showed that administration of lactic-acid-producing bacteria-type symbionts significantly increased expansion of intestinal stem cells (ISCs), paneth cells, and goblet cells. Lactate stimulated ISC proliferation through Wnt/β-catenin signals of paneth cells and intestinal stromal cells. [Cell Host Microbe] Abstract | Graphical Abstract

Mouse Fetal Intestinal Organoids: New Model to Study Epithelial Maturation from Suckling to Weaning

The authors showed that organoids derived from mouse primary fetal intestinal epithelial cells expressed markers of late fetal and neonatal development. In a stable culture medium, these fetal epithelium‐derived organoids lost all markers of neonatal epithelium and started expressing hallmarks of adult epithelium in a time frame that mirrored epithelial maturation in vivo. [EMBO Rep] Full Article | Graphical Abstract

Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis

Investigators report that inflammation induced the accumulation of CD11b⁺Gr1⁺ myeloid-derived suppressor cells that expressed high levels of IL-10 in colon tissue. IL-10 induced the activation of STAT3 that directly bound to the Dnmt1 and Dnmt3b promoters to activate their expression, resulting in DNA hypermethylation at the Irf8 promoter to silence IRF8 expression in colon epithelial cells. [Cell Rep] Full Article | Graphical Abstract

HSP110 Translocates to the Nucleus upon Genotoxic Chemotherapy and Promotes DNA Repair in Colorectal Cancer Cells

Scientists showed in vitro, in vivo, and in patients’ biopsies that HSP110 co-localized with DNA damage. In colorectal cancer cells, HSP110 translocated into the nucleus upon treatment with genotoxic chemotherapy such as oxaliplatin. [Oncogene] Abstract

YAP1-Induced MALAT1 Promotes Epithelial-Mesenchymal Transition and Angiogenesis by Sponging miR-126-5p in Colorectal Cancer

Yes-associated protein 1 (YAP1) promoted proliferation, invasion, and migration in colon cancer cells, in vitro and in vivo. MALAT1 was expressed, with differential expression of 11 lncRNAs in HCT116 cells after transfection with siYAP1 or si-Ctl. [Oncogene] Full Article

IL-10 Signaling Prevents Gluten-Dependent Intraepithelial CD4⁺ Cytotoxic T Lymphocyte Infiltration and Epithelial Damage in the Small Intestine

Researchers demonstrated that interleukin-10 (IL-10) regulation prevented gluten-induced cytotoxic inflammatory intraepithelial lymphocyte infiltration. IL-10 suppressed gluten-dependent small intestinal epithelial hyperproliferation and upregulation of stress-induced molecules on epithelial cells. [Mucosal Immunol] Abstract

Dichloroacetate and Salinomycin Exert a Synergistic Cytotoxic Effect in Colorectal Cancer Cell Lines

The authors examined a hypothesis that dichloroacetate, a metabolic inhibitor, might efficiently potentiate the cytotoxic effect of salinomycin, an antibiotic ionophore, on two human colorectal cancer derived cell lines DLD-1 and HCT116. [Sci Rep] Full Article

Reversible Senescence of Human Colon Cancer Cells after Blockage of Mitosis/Cytokinesis Caused by the CNF1 Cyclomodulin from Escherichia coli

Researchers showed that cytotoxic necrotizing factor 1 (CNF1) treatment blocked mitosis/cytokinesis, elicited endoreplication and polyploidisation in cultured human colon cancer cells, and drove them into reversible senescence, which provided a survival route for cells via depolyploidisation. [Sci Rep] Full Article

Berberine Reversed the Epithelial‐Mesenchymal Transition of Normal Colonic Epithelial Cells Induced by SW480 Cells through Regulating the Important Components in the TGF‐β Pathway

Scientists found that colon cancer cells SW480 induced spindle‐like morphological changes and downregulation of E‐cadherin and upregulation of vimentin and alpha‐smooth muscle actin in colon epithelial cells HCoEpiCs by using transwell coculture system and conditioned medium from SW480. [J Cell Physiol] Abstract

The mTORC1 Signaling Modulated by Intracellular C3 Activation in Paneth Cells Promotes Intestinal Epithelial Regeneration during Acute Injury

Exogenous C3 by itself failed to promote the growth of intestinal epithelium, but distinctly enhanced the activity of paneth cells via intracellular activation, which subsequently supported the expansion of intestinal stem cells inside of intestinal crypts. [Int Immunopharmacol] Abstract

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Exosomes as a Novel Cell‐Free Therapeutic Approach in Gastrointestinal Diseases

The authors consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell‐free therapeutic approach in gastrointestinal diseases like inflammatory bowel disease, gastric cancer, and colon cancer. [J Cell Physiol] Abstract

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Cancer Prevention Pharmaceuticals Announces Last Patient Completes Phase III Trial Protocol of CPP-1X/sul for Familial Adenomatous Polyposis

Cancer Prevention Pharmaceuticals, Inc. announced the last patient has completed the study protocol in its pivotal Phase III trial of CPP-1X/sul for adults with familial adenomatous polyposis, a rare genetic disease that, if left untreated, progresses to colorectal cancer in nearly 100% of patients. [Cancer Prevention Pharmaceuticals, Inc. (Business Wire, Inc.)] Press Release

Immix Observes Clinical Benefit at Dose-Level 2 in Phase Ib Clinical Trial in Refractory Cancer

Immix Biopharma, Inc announced positive interim results from its ongoing Phase Ib/IIa study testing IMX-110 in advanced solid tumors. Immix observed Stable Disease at cohort 2 in a middle-aged male with stage IV colorectal cancer that was refractory to radiation therapy, chemotherapy and immunotherapy. [Immix Biopharma, Inc] Press Release

Dr. James Wells presents his group’s work on hPSC-derived GI organoids and their use for studying disease. Watch Now

The End of DACA Would Be a Blow to Science

With the end of Deferred Action for Childhood Arrivals (DACA), undocumented scientists will lose what few protections they currently have under immigrant law, lose their access to their scientific research, and once again live in fear, as they are caught in legal limbo. [Scientific America] Editorial

South Korean Scientists Protest Treatment of University President Accused of Misusing Funds

Researchers in South Korea have criticized the nation’s science ministry for its handling of an investigation into the president of the Korea Advanced Institute of Science and Technology (KAIST) in Daejon, the country’s top technical university. The science ministry alleges that KAIST leader Shin Sung-Chul made illegal payments to a California lab, but many scientists see a political purge. [Nature News] Editorial

Lawsuit Alleges NIH, FDA Let Clinical Trial Sponsors Off the Hook

A former top official at the FDA and a longtime science journalist are suing the agency and the National Institutes of Health (NIH), saying they let clinical trial sponsors off the hook for reporting nearly a decade’s worth of important scientific data. [STAT News] Editorial

NEW 2019 ASCO Annual Meeting
May 31-June 4, 2019
Chicago, Illinois, United States

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NEW Research Fellow – Mucosal Immunology (University of Edinburgh)

Postdoctoral Associate – Colon Cancer (Baylor College of Medicine)

Faculty Position – Cancer Cell Signaling (The University of New Mexico Comprehensive Cancer Center)

Postdoctoral Position – Cancer Genomics and Precision Oncology (Memorial Sloan Kettering Cancer Center)

PhD Scholarship – Biophysical Nanomedicine (Technical University of Denmark)

Postdoctoral Scientist – Intestinal Immunology (University of Oxford)

Postdoctoral Researcher – Pesticide Exposure and Effects on Colorectal Cancer (Luxembourg Institute of Health)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Fellow – Intestinal & Colonic Stem Cell Research (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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