Intestinal Cell News Volume 6.03 | Jan 31 2020

TOP STORY

Vibrio cholerae-Symbiont Interactions Inhibit Intestinal Repair in Drosophila

Scientists found that the enteric pathogen V. cholerae blocked critical growth and differentiation pathways in Drosophila progenitors, despite extensive damage to epithelial tissue. They showed that the inhibition of epithelial repair required interactions between the V. cholerae type six secretion system and a community of common symbiotic bacteria, as elimination of the gut microbiome was sufficient to restore homeostatic growth in infected intestines. [Cell Rep] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Human BCL-G Regulates Secretion of Inflammatory Chemokines but Is Dispensable for Induction of Apoptosis by IFN-γ and TNF-α in Intestinal Epithelial Cells

The authors analyzed gastrointestinal expression of human BCL-G in health and disease states, and investigated its contribution to inflammation-induced tissue damage by exposing intestinal epithelial cells to IFN-γ and TNF-α, two pro-inflammatory mediators associated with gut immunopathology. [Cell Death Dis] Full Article

The Long Noncoding RNA TUG1 Is Required for TGF-β/TWIST1/EMT-Mediated Metastasis in Colorectal Cancer Cells

Investigators showed that transforming growth factor-beta (TGF-β) promoted colorectal cancer (CRC) migration and upregulated the expression of long-noncoding RNA taurine upregulated gene 1 (TUG1). TUG1 knockdown inhibited migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells in vitro, and reduced CRC lung metastasis in vivo. [Cell Death Dis] Full Article

CD147 Promotes Cell Small Extracellular Vesicles Release during Colon Cancer Stem Cells Differentiation and Triggers Cellular Changes in Recipient Cells

Researchers showed that small extracellular vesicle (sEV) secretion during colon cancer stem cell differentiation was partially controlled by CD147, a well-known player involved in colon cancer tumorigenesis. CD147 + sEVs activated a signaling cascade in recipient cells inducing molecular invasive features in colon cancer cells. [Cancers] Full Article

Novel Nano-Vehicle for Delivery and Efficiency of Anticancer Auraptene against Colon Cancer Cells

Scientists devised, prepared and characterized nano encapsulated auraptene and evaluated cytotoxic and apoptotic effects on HT-29 colon cancer cells. [Sci Rep] Full Article

Activation of pH-Sensing Receptor OGR1 (GPR68) Induces ER Stress Via the IRE1α/JNK Pathway in an Intestinal Epithelial Cell Model

Caco-2 cells stably overexpressing ovarian cancer G-protein coupled receptor (OGR1) were subjected to an acidic pH shift. pH-dependent OGR1-mediated signaling led to a significant upregulation in the endoplasmic reticulum (ER) stress markers, binding immunoglobulin protein and phospho-inositol required 1α (IRE1α), which was reversed by a novel OGR1 inhibitor and a c-Jun N-terminal kinase (JNK) inhibitor. [Sci Rep] Full Article

Nuclear-Localized Costimulatory Molecule 4-1BBL Promotes Colon Cancer Cell Proliferation and Migration by Regulating Nuclear Gsk3β, and Is Linked to the Poor Outcomes Associated with Colon Cancer

4-1BBL knockout (KO) arrested the proliferation and impaired the migration and invasion ability of colon cancer cells in vitro and retarded tumor growth in vivo. 4-1BBL KO increased the accumulation of Gsk3β in the nuclei of colon cancer cells and consequently decreased the expression of Wnt pathway target genes and thus altered tumor biological behavior. [Cell Cycle] Abstract

Silencing of Long Noncoding RNA UCA1 Inhibits Colon Cancer Invasion, Migration and Epithelial‐Mesenchymal Transition and Tumor Formation by Upregulating miR‐185‐5p In Vitro and In Vivo

The authors explored the molecular mechanism of urothelial carcinoma‐associated 1 (UCA1) in the development of colon cancer from both in vitro and in vivo. They showed that UCA1 was highly expressed in colon cancer cells, while miR‐185‐5p was low expressed. [Cell Biochem Funct] Abstract

A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer

Researchers observed that miR-143 was lowly expressed in patients with colorectal cancer. The up-regulation of miR-143 inhibited cell proliferation and induced cell apoptosis by targeting KRAS in colorectal cancer cells. [Mol Ther Oncolytics] Abstract

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Microbial Metabolites & Intestinal Stem Cells Tune Intestinal Homeostasis

The authors survey the literature on gut microbiota‐host crosstalk, highlighting the effects of gut microbial metabolites on intestinal stem cells. They discuss the production of various classes of metabolites, their actions on intestinal stem cells and, finally, comment on how the production and function of metabolites are modulated by aging and dietary intake. [Proteomics] Abstract

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Phase II DESTINY-Gastric01 Trial of DS-8201 versus Chemotherapy Met Primary Endpoint

Daiichi Sankyo Company, Limited and AstraZeneca announced positive topline results from the pivotal Phase II DESTINY-Gastric01 trial of DS-8201, a HER2 directed antibody drug conjugate, in patients with HER2 positive unresectable or metastatic gastric or gastroesophageal junction cancer that had progressed following two or more treatment regimens including trastuzumab and chemotherapy. [Daiichi Sankyo Company, Limited] Press Release

Syros Announces First Patient Dosed in Phase I Clinical Trial of SY-5609, Its Highly Selective and Potent Oral CDK7 Inhibitor, in Patients with Select Solid Tumors

Syros Pharmaceuticals announced that the first patient has been dosed in the Phase I clinical trial of SY-5609, its highly selective and potent oral cyclin-dependent kinase 7 (CDK7) inhibitor. The trial is enrolling patients with advanced breast, colorectal, lung or ovarian cancer, or with solid tumors of any histology that harbor Rb pathway alterations. [Syros Pharmaceuticals] Press Release

Most Innovative Cancer Drugs Take Too Long to Reach Patients in the UK

Despite giddy advances in treating cancer, a new analysis finds needed medicines have been reaching patients in the UK more slowly, and that both drug makers and government agencies are to blame. [STAT News] Editorial

NIH’s New Cluster Hiring Program Aims to Help Schools Attract Diverse Faculty

The National Institutes of Health (NIH) is hoping universities will use a controversial, and largely untested, method of hiring junior faculty members to improve the diversity of the US biomedical research workforce. [ScienceInsider] Editorial

NEW A Gut-Systemic Perspective for Metabolic Disease
March 22-26, 2020
Santa Fe, New Mexico, United States

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NEW 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)

Researcher – Synthetic Ecology of Human Gut Microbiota (Flanders Institute for Biotechnology)

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

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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