Intestinal Cell News Volume 5.06 | Feb 22 2019

TOP STORY

FXR Regulates Intestinal Cancer Stem Cell Proliferation

Researchers showed that bile acids that antagonize intestinal farnesoid X receptor (FXR) function, including tauro-β-muricholic acid and deoxycholic acid, induced proliferation and DNA damage in Lgr5-expressing (Lgr5⁺) cells. Conversely, selective activation of intestinal FXR could restrict abnormal Lgr5⁺ cell growth and curtail colorectal cancer progression. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

DUB3 Deubiquitinates and Stabilizes NRF2 in Chemotherapy Resistance of Colorectal Cancer

Coimmunoprecipitation studies revealed interactions between nuclear factor (erythroid-derived 2)-like 2 (NRF2) and deubiquitinase 3 (DUB3), as well as between KEAP1 and DUB3, indicating that NRF2, DUB3, and KEAP1 formed a large functional complex. Importantly, ectopic expression of DUB3 caused NRF2-dependent chemotherapy resistance in colon cancer cell lines. [Cell Death Differ] Abstract

mIR-1265 Regulates Cellular Proliferation and Apoptosis by Targeting Calcium Binding Protein 39 in Gastric Cancer and, Thereby, Impairing Oncogenic Autophagy

The knockdown of autophagy-related gene 12 impaired the effects of miR-1265 inhibition or calcium binding protein 39 overexpression in gastric cancer (GC). miR-1265 also suppressed the growth of GC cells in vivo and that of human gastric organoids. [Cancer Lett] Full Article

Knockdown IGF-1R Triggers Viral RNA Sensors MDA5- and RIG-I-Mediated Mitochondrial Apoptosis in Colonic Cancer Cells

Insulin-like growth factor-1 receptor (IGF-1R) knockdown-triggered MDA5 and RIG-I was investigated in human colonic cancer cells. Increased MDA5 and RIG-I were clearly seen in the cytoplasm in cancer cells as well as normal human colonic cells silenced IGF-1R. Notably, the upregulation of MDA5 and RIG-I was not affected by blockage of the PI3K/Akt pathway with LY294002. [Mol Ther Nucleic Acids] Abstract | Full Article

ATXN2L Upregulated by Epidermal Growth Factor Promotes Gastric Cancer Cell Invasiveness and Oxaliplatin Resistance

In gastric cancer (GC) cells, ataxin-2-like (ATXN2L) expression was knocked down and functional experiments were performed. ATXN2L promoted GC cell migration and invasion via epithelial to mesenchymal transition, yet no influence on proliferation was detected by ATXN2L interference. [Cell Death Dis] Full Article

Goat and Buffalo Milk Fat Globule Membranes Exhibit Better Effects at Inducing Apoptosis and Reduction the Viability of HT-29 Cells

All milk fat globule membranes (MFGMs) reduced cellular viability which was in agreement with cell morphology and apoptosis. However, the number of cells in S-phase from 24 hours to 72 hours was increased significantly by treatment with goat, buffalo and bovine MFGMs, but not yak and camel. [Sci Rep] Full Article

An FBXW7-ZEB2 Axis Links EMT and Tumor Microenvironment to Promote Colorectal Cancer Stem Cells and Chemoresistance

Using a modified yeast-2-hybrid system and 2D gel-based proteomics methods, Investigators showed that the E3-ubiquitin ligase FBXW7 directly bound and degraded the epithelial-mesenchymal transition (EMT)-inducing transcription factor ZEB2 in a phosphorylation-dependent manner. [Oncogenesis] Full Article

Innate Lymphoid Cell Type 3-Derived Interleukin-22 Boosts Lipocalin-2 Production in Intestinal Epithelial Cells via Synergy between STAT3 and NF-kB

Scientists demonstrated how IL-22-induced activation of STAT3 synergized with NF-kB-activating cytokines to enhance lipocalin-2 (LCN-2) expression in human intestinal epithelial cells and elucidated how innate lymphoid cells type 3 were involved in LCN-2-mediated host defense against Enterobacteriaceae. [J Biol Chem] Abstract | Full Article

Combinatorial Effect of Blueberry Extracts and Oxaliplatin in Human Colon Cancer Cells

Flow cytometry analysis indicated that treatment with the blueberry extracts, oxaliplatin or in combination could induce G0/G1 cell cycle arrest, apoptosis, increase of reactive oxygen species, and induced loss of mitochondrial membrane potential in HCT-116 cells. [J Cell Physiol] Abstract

Rhein from Rheum Rhabarbarum Inhibits Hydrogen Peroxide-Induced Oxidative Stress in Intestinal Epithelial Cells Partly through PI3K/Akt-Mediated Nrf2/HO-1 Pathways

H2O2-challenged IEC-6 cells were incubated in the pretreatment with or without rhein or LY294002, a PI3K/Akt inhibitor. The cell viability, apoptosis, intracellular ROS and antioxidants were measured. The expressions of heme oxygenase-1 (HO-1), nuclear NF-erythroid 2-related factor (Nrf2), Akt and p-Akt were evaluated by western blotting. [J Agric Food Chem] Abstract

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Redefining the IBDs Using Genome-Scale Molecular Phenotyping

The authors posit that genome-scale molecular phenotyping in large cohorts holds great promise not only to further the understanding of the diverse molecular causes of IBD but also for improving clinical trial design to develop more personalized disease management and treatment. [Nat Rev Gastroenterol Hepatol] Abstract

Cancer-Associated Fibroblasts in Gastrointestinal Cancer

Investigators outline the emerging understanding of gastrointestinal cancer-associated fibroblasts with a particular emphasis on their origin and heterogeneity, as well as their function in cancer cell proliferation, tumor immunity, angiogenesis, extracellular matrix remodeling and drug resistance. [Nat Rev Gastroenterol Hepatol] Abstract

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Innovent Announces a Collaboration with Chipscreen Biosciences to Evaluate the Combination Therapy in Colorectal Cancer Patients

Innovent Biologics, Inc. announced the signing of a collaboration agreement with Shenzhen Chipscreen Biosciences Co., Ltd. to evaluate the safety and tolerability of the combination therapy of Innovent’s Tyvyt^®, a fully human anti-programmed cell death protein 1 monoclonal antibody and IBI305, a biosimilar product candidate of bevacizumab and a recombinant humanized anti-vascular endothelial growth factor monoclonal antibody, with Chipscreen Biosciences’ Chidamide, a benzamide-based selective inhibitor of class I and IIb histone deacetylases, in patients with advanced colorectal cancer. [Innovent Biologics, Inc.] Press Release

Nearly $20 Million Awarded by CPRIT to MD Anderson

The University of Texas MD Anderson Cancer Center was awarded $19.6 million from the Cancer Prevention and Research Institute of Texas (CPRIT) to support research, recruitment and prevention efforts. In total, MD Anderson and its projects received 20 percent of the $96 million in awards announced by CPRIT. [The University of Texas MD Anderson Cancer Center] Press Release

Koutif Therapeutics Announces FDA Acceptance of IND Application for Novel New Treatment of IBD

Koutif Therapeutics announced that its investigational new drug (IND) application for KT-1002 has been cleared by the FDA to begin a Phase I clinical trial for the treatment of IBD, including ulcerative colitis and Crohn’s Disease. The Phase I clinical trial will aim to characterize human exposures, metabolism, and safety to inform selection of the optimal dose of KT-1002. [Koutif Therapeutics] Press Release

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

Open-Access Pioneer Randy Schekman on Plan S and Disrupting Scientific Publishing

Nobel laureate Randy Schekman shook up the publishing industry when he launched the open-access journal eLife in 2012. Armed with millions in funding from three of the world’s largest private biomedical charities — the Wellcome Trust, the Max Planck Society and the Howard Hughes Medical Institute — Schekman designed the journal to compete with publishing powerhouses such as Nature, Science and Cell. [Nature News] Editorial

Foreign Governments Want to Boost Their Biotech Industries — So They’re Setting Up Shop in Boston

Cities and states around the corner and around the country have angled for years to set themselves up as the next Kendall Square, hoping to import some of the magic of Boston’s biotech hub and its job-creating economic engine. Increasingly, foreign governments are pushing for the same. [STAT News] Editorial

NEW Keystone Symposia: Cancer Stem Cells – Advances in Biology and Clinical Translation
October 13-17, 2019
Hong Kong, China

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NEW PhD Research Fellowship – Pathogenesis of Celiac Disease (University of Oslo)

Postdoctoral Researcher Positions – Intestinal Epithelial Barrier in Autoimmune Diseases (BioMed X Innovation Center)

Faculty Position- General Gastroenterology (Oregon Health and Science University)

Postdoctoral Research Scientist – Intestinal Stem Cell Biology (Columbia University)

Assistant Professor – Basic and Translational Cancer Research (Texas Tech University Health Sciences Center)

Advanced Research Assistant – Inflammatory Bowel Disease Research (Wellcome Sanger Institute)

Research Associate – Infections, Inflammation & Colorectal Cancer (Imperial College of London)

Postdoctoral Position – Colon Cancer (Vanderbilt University)

Postdoctoral Research Opportunities – Cancer Center Program (Albert Einstein College of Medicine of Yeshiva University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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