Intestinal Cell News Volume 4.30 | Aug 10 2018

TOP STORY

Divergent Routes toward Wnt and R-Spondin Niche Independency during Human Gastric Carcinogenesis

Phenotype analyses of gastric cancer organoids revealed divergent genetic and epigenetic routes to gain Wnt and R-spondin niche independency. Researchers identified a significant association between CDH1/ TP53 compound mutations and the R-spondin independency that was functionally validated by CRISPR-based knockout. [Cell] Abstract | Graphical Abstract

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Melatonin and 5-Fluorouracil Co-Suppress Colon Cancer Stem Cells by Regulating Cellular Prion Protein-Oct4 Axis

In colorectal cancer stem cells, PRNP overexpression protectd Oct4 against inhibition by 5-fluorouracil and melatonin. In contrast, Nanog, Sox2, and ALDH1A1 had no such protection. [J Pineal Res] Abstract

Improving Anticancer Activity towards Colon Cancer Cells with a New p53-Activating Agent

In HCT116 cells, SYNAP displayed p53-dependent growth inhibitory effect, associated with cell cycle arrest and apoptosis, anti-migratory activity and regulation of the expression levels of p53 transcriptional targets. Moreover, SYNAP sensitized colon cancer cells to the cytotoxic effect of conventional chemotherapeutics. [Br J Pharmacol] Abstract

DBC1 Regulates Wnt/β-Catenin-Mediated Expression of MACC1, a Key Regulator of Cancer Progression, in Colon Cancer

Scientists reported that metastasis-associated in colon cancer 1 (MACC1) is a direct target of Wnt/β-catenin signaling pathway in colon cancer cells and that DBC1 functioned as a coactivator for Wnt-mediated MACC1 expression by promoting the activity of a LEF1/β-catenin-dependent enhancer located in intron 1 of the MACC1 gene. [Cell Death Dis] Full Article

Interferon Gamma Decreases Intestinal Epithelial Aquaporin 3 Expression through Downregulation of Constitutive Transcription

Knockdown of signal transducer and activator of transcription 1 (STAT1) partially prevented the interferon gamma (IFNγ)-induced downregulation of aquaporin (AQP3) expression, whereas STAT3 and Sp3 knockdowns resulted in increased baseline expression of AQP3 but did not alter IFNγ-induced downregulation. [J Mol Med] Abstract

Transcriptional and Proteomic Analysis Revealed a Synergistic Effect of Aflatoxin M1 and Ochratoxin a Mycotoxins on Intestinal Epithelial Integrity of Differentiated Human Caco-2 Cells

Integrated transcriptome and proteome analysis of aflatoxin M1 and pochratoxin A, alone or in combination, indicated synergistic effect of the two mycotoxins in disrupting intestinal integrity. This effect was mechanistically linked to a broad range of pathways related to intestinal integrity enriched by down-regulated genes and proteins, associated to focal adhesion, adherens junction, and gap junction pathways. [J Proteome Res] Abstract

The Atypical Cyclin CNTD2 Promotes Colon Cancer Cell Proliferation and Migration

CNTD2 overexpression in colorectal cancer (CRC) cell lines increased their proliferation capacity and migration, as well as spheroid formation capacity and anchorage-independent growth. CNTD2 increased tumor growth in vivo on xenograft models of CRC with wild-type BRAF. [Sci Rep] Full Article

Reversine Inhibits Colon Carcinoma Cell Migration by Targeting JNK1

Investigators found that the small molecule reversine reduced the migration potential of human colon carcinoma cells in vitro. They identified the c-Jun N-terminal kinase (JNK) cascade as the main pathway inhibited by reversine. Knockdown experiments and pharmacological inhibition identified JNK1 but not JNK2, as a downstream effector target in cancer cell migration. [Sci Rep] Full Article

Mitochondria-Targeted Drugs Stimulate Mitophagy and Abrogate Colon Cancer Cell Proliferation

3-Carboxy proxyl nitroxide (Mito-CP) and Mito-Metformin released Unc-51-like autophagy-activating kinase 1 from mTOR-mediated inhibition, affected mitochondrial morphology, and decreased mitochondrial membrane potential, all indicators of mitophagy. Pharmacological inhibition of the AMP-activated kinase signaling cascade mitigated the anti-proliferative effects of Mito-CP and Mito-Metformin. [J Biol Chem] Abstract | Full Article

Vitamin D Deficiency Has a Negative Impact on Cetuximab-Mediated Cellular Cytotoxicity against Human Colon Carcinoma Cells

Blood samples were obtained from 124 healthy volunteers and serum vitamin D was determined by RIA. NK cells were isolated from each sample and added to human colorectal carcinoma cells with or without cetuximab, and antibody-dependent cell-mediated cytotoxicity was assessed using a colorimetric lactate dehydrogenase assay. [Target Oncol] Abstract

Screening Method for Anti-Colon Cancer Drugs Using Two Sensor Cell Lines with Human β4-Galactosyltransferase 4 Gene Promoters

To develop a screening method for anti-colon cancer drugs, two sensor cell lines having the luciferase gene under the control of two β4-galactosyltransferase 4 gene promoters that differed in length were established from SW480 human colon cancer cells. [Sensors (Basel)] Full Article

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Rebuilding the Gut Microbiota Ecosystem

Gut microbiota dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. The authors discuss the various aspects of these strategies to counteract intestinal dysbiosis. [Int J Environ Res Public Health] Full Article

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Salix, Cedars-Sinai Partner on Gut Microbiome-Related GI Treatments

Salix Pharmaceuticals said it will partner with Cedars-Sinai Medical Center to discover new treatments for gastrointestinal (GI) disorders related to conditions of the gut microbiome, through a collaboration whose value was not disclosed. [Salix Pharmaceuticals (Genetic Engineering & Biotechnology News)] Press Release

Array BioPharma Receives FDA Breakthrough Therapy Designation for BRAFTOVI^™ in Combination with MEKTOVI^® and Cetuximab for BRAFV600E-Mutant Metastatic Colorectal Cancer

Array BioPharma Inc. announced it has received Breakthrough Therapy Designation from the U.S. FDA for encorafenib, in combination with binimetinib and cetuximab for the treatment of patients with BRAFV600E-mutant metastatic colorectal cancer as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease. [Array BioPharma] Press Release

Synergy Pharmaceuticals Announces License Agreement with Luoxin Pharmaceutical Group for TRULANCE^® (Plecanatide) in China

Synergy Pharmaceuticals Inc. announced that the company has entered into a license agreement with Luoxin Pharmaceutical Group Co., Ltd., Shandong providing Luoxin exclusive rights to develop and commercialize Synergy’s lead product TRULANCE^® for the treatment of adults with chronic idiopathic constipation and irritable bowel syndrome with constipation in mainland China, Hong Kong and Macau. [Synergy Pharmaceuticals Inc.] Press Release

Stem Cell Transplants to Be Used in Treating Crohn’s Disease

A clinical trial has begun which will use stem cell transplants to grow a new immune system for people with untreatable Crohn’s disease – a painful and chronic intestinal disease which affects at least 115,000 people in the UK. [Queen Mary University of London] Press Release

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

US Congress Leaves Science Agencies Hanging — Again

Lawmakers in the US Congress are running out of time to pass a budget for the 2019 fiscal year, and have yet to resolve major disagreements over climate-change and environment programs. [Nature News] Editorial

Gottlieb: FDA Will Streamline Drug Safety Evaluations

The FDA will soon standardize the way it handles data on the safety and effectiveness of drugs in an effort to reduce inconsistencies in the drug review process. [STAT News] Editorial

India Cracks Down on Plagiarism at Universities

India has for the first time introduced regulations to detect and punish acts of plagiarism at universities. Punishments for researchers or students caught breaking the rules range from requiring that a manuscript be withdrawn to sacking or expulsion, depending on the extent of the plagiarism. [Nature News] Editorial

Embattled French Health-Agency Chief Withdraws Leadership Bid

The chief of France’s national biomedical-research agency INSERM has said that he will not run for a second term, a decision that ends months of uncertainty about his future at the organization. [Nature News] Editorial

NEW Tumor Immunology and Immunotherapy
November 27-30, 2018
Miami, Florida, United States

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NEW Postdoctoral Position – Host-Microbiome Interactions in the Gastrointestinal Tract (University of Gothenburg)

Postdoctoral Associate – Functional Genomics of Inflammatory Bowel Disease (Center for Computational and Integrative Biology)

Postdoctoral Fellow – Signal Transduction of Intestinal Cells (Mornell Chemical Senses Center)

Postdoctoral Fellow – Colon Cancer (Vanderbilt University Medical Center)

Senior Research Scientist – Cancer Research (Memorial Sloan Kettering Cancer Center)

Assistant/Associate Research Professor – Inflammatory Bowel Disease (Cedars-Sinai Inflammatory Bowel & Immunobiology Research Institute)

Assistant Professor – Intestinal Physiology & Epithelial Cell Biology (Boston Children’s Hospital/Harvard Medical School)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

Postdoctoral Scholar – Molecular and Cell Biology (University of California, Berkeley)

Assistant Professor – Cancer Biology (Université de Genève)

Postdoctoral Fellow – Colorectal Cancer (Dalhousie University)

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