Intestinal Cell News Volume 3.33 | Sep 1 2017

TOP STORY

Fine-Tuning and Autoregulation of the Intestinal Determinant and Tumor Suppressor Homeobox Gene CDX2 by Alternative Splicing

Functional studies revealed a dominant-negative effect exerted by miniCDX2 on the transcriptional activity of CDX2, and conversely similar effects regarding several transcription-independent functions of CDX2. A regulatory role played by the CDX2 and miniCDX2 homeoproteins on their pre-mRNA splicing was displayed through interactions with splicing factors. [Cell Death Differ] Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Berberine Binds RXRα to Suppress β-Catenin Signaling in Colon Cancer Cells

The authors provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binds to and synergistically activates RXRα with 9-cis-retinoic acid, a natural ligand binding to the classical ligand-binding pocket of RXRα. [Oncogene] Full Article

Nuclear Factor E2-Related Factor-2 Has a Differential Impact on MCT1 and MCT4 Lactate Carrier Expression in Colonic Epithelial Cells: A Condition Favoring Metabolic Symbiosis between Colorectal Cancer and Stromal Cells

Investigators elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells. [Oncogene] Abstract

Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells

Scientists used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average enabled the de novo construction of a functional protein correlation network, which ultimately exposed the collateral effects of mutations on protein complexes. [Cell Rep] Full Article | Press Release | Graphical Abstract

Short Chain Fatty Acids Enhance Aryl Hydrocarbon (Ah) Responsiveness in Mouse Colonocytes and Caco-2 Human Colon Cancer Cells

Ah receptor ligands are important for gastrointestinal health and play a role in gut inflammation and the induction of T regulatory cells, and the short chain fatty acids butyrate, propionate and acetate also induce similar protective responses. Studies with butyrate demonstrated that this compound significantly increased expression of Ah-responsive genes such as Cyp1a1/CYP1A1 in YAMC mouse colonocytes and Caco-2 human colon cancer cell lines. [Sci Rep] Full Article

FOXD3 Regulates CSC Marker, DCLK1-S, and Invasive Potential: Prognostic Implications in Colon Cancer

Researchers examined if the transcriptional activity of the (β)-promoter is suppressed in normal-vs-cancerous cells. Based on in silico and molecular approaches, it was discovered that FOXD3 potently inhibits the transcriptional activity of the (β)-promoter. [Mol Cancer Res] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells

Scientists report the in vitro generation of enterospheres (hEnS) from human pluripotent stem cell-derived gastrointestinal epithelial precursors. hEnS are cystic spheroids with a simple uniform structure composed entirely of intestinal epithelium. hEnS expressed markers of mature brush border cells and share a transcriptome profile similar to that of more mature intestinal organoids. [Stem Cell Reports] Full Article

Intestinal Stem Cells Contribute to the Maturation of the Neonatal Small Intestine and Colon Independently of Digestive Activity

Researchers report a novel system for the allotransplantation of small intestine and colon harvested from Lgr5^{EGFP–IRES–CreERT2/+}; Rosa26^rbw/+ mice immediately after birth into the subrenal capsule of wild-type mice. The intestinal stem cells in transplanted tissues were shown to self-renew and produce progeny, resulting in the descendants of the stem cells occupying the crypt-villus unit of the small intestine or the whole crypt of the colon. [Sci Rep] Full Article

Aging Effects on Intestinal Homeostasis Associated with Expansion and Dysfunction of Intestinal Epithelial Stem Cells

Investigators tested the hypothesis that aging promotes intestinal epithelial stem cell (IESC) dysfunction using old and young Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permitted analyses of active IESC, activatable reserve IESC and enteroendocrine cells, Sox9-EGFP^Sublow progenitors, and Sox9-EGFP^Negative differentiated lineages. [Aging (Albany NY)] Full Article

Intestinal Hypoxia and Hypoxia-Induced Signaling as Therapeutic Targets for IBD

The authors discuss the involvement of mucosal hypoxia and hypoxia-induced signaling in the pathogenesis of IBD and elaborate in detail on the role of hypoxia-inducible factors , nuclear factor-κB and prolyl hydroxylases in different cell types during intestinal inflammation. [Nat Rev Gastroenterol Hepatol] Abstract

Enteroendocrine Cells-Sensory Sentinels of the Intestinal Environment and Orchestrators of Mucosal Immunity

Scientists introduce enteroendocrine chemosensory roles, summarize studies correlating enteroendocrine perturbations with intestinal inflammation and describe the mechanistic interactions by which enteroendocrine and mucosal immune cells interact during disease, highlighting this immunoendocrine axis as a key aspect of innate immunity. [Mucosal Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Array Biopharma to Present BEACON CRC Safety Lead-In and COLUMBUS Part 2 Results

Array BioPharma Inc. announced that results from the Phase III BEACON CRC safety lead-in study in BRAF-mutant colorectal cancer and the Phase III COLUMBUS Part 2 study in BRAF-mutant melanoma will be presented. [Press release from Array BioPharma Inc. discussing research to be presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

Symphogen Presents Sym004 Phase II Data

Symphogen announced that the promising data from its Phase II study with Sym004, a mAb mixture targeting EGFR, has been selected for oral presentation. [Press release from Symphogen discussing research to be presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

Outstanding Investigator Grant Awarded to Dario C. Altieri, M.D., Wistar President and CEO

The Wistar Institute announced that distinguished scientist Dario C. Altieri, M.D., Wistar president and CEO and director of the Institute’s Cancer Center, has been awarded an Outstanding Investigator Grant by the National Institutes of Health for high-caliber research exploring “tumor plasticity.” This highly coveted NCI program grant totals nearly $8 million over seven years. [The Wistar Institute] Press Release

Dr. Peter Glazer Receives Prestigious Outstanding Investigator Award for Cancer Research

The National Cancer Institute has named Peter M. Glazer, M.D., Ph.D., as a recipient of its Outstanding Investigator Award. Glazer is the Robert E. Hunter Professor of Therapeutic Radiology, professor of genetics and chairman of the department of Therapeutic Radiology at Yale School of Medicine and Yale Cancer Center. [Yale School of Medicine] Press Release

Imugene Commences First Patient Dosing of HER-Vaxx Phase Ib/II Gastric Cancer Study

Imugene Limited announced that it has commenced first patient dosing of the Phase Ib/II clinical study of its HER-Vaxx immunotherapy in gastric cancer. [Imugene Limited] Press Release

Science Suffers as China’s Internet Censors Plug Holes in Great Firewall

China is tightening the screws on internet access, again. The latest crackdown—an evolving effort to ban virtual private networks not under government control—could seriously erode scientists’ ability to stay connected with peers abroad. [ScienceInsider] Editorial

Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine

The FDA has taken steps in Florida and California to address a number of especially troubling products being marketed. But unfortunately, these are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk. [U.S. Food and Drug Administration] Editorial

FDA Warns US Stem Cell Clinic of Significant Deviations

The FDA posted a warning letter issued to US Stem Cell Clinic of Sunrise, Florida, and its Chief Scientific Officer Kristin Comella for marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. [U.S. Food and Drug Administration] Editorial

NEW 25^th Biennial Congress of the European Association for Cancer Research (EACR)
June 30-July 3, 2018
Amsterdam, Netherlands

Visit our events page to see a complete list of events in the community.

NEW PhD Studentship – Gastrointestinal Physiology/Epithelial Biology (Royal College of Surgeons in Ireland)

NEW Research Assistant – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Postdoctoral Training Fellow – Systems and Precision Cancer (Institute of Cancer Research)

Postdoctoral Research Associate – Intestinal Fibroblast Subsets (University of Oxford)

Postdoctoral Position – Epigenetic Dysregulation in Cancer Progression (University of Florida)

Research Associate – Colorectal Cancer (University College London)

Research Postdoctoral Fellow – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Postdoctoral Fellow – Gut Microbiota and Colon Cancer (University of Toronto)

Postdoctoral Position – Inflammation and Cancer (Brigham & Women’s Hospital – Harvard Medical School)

Postdoctoral Research Fellow – Cancer Epidemiology (Fred Hutchinson Cancer Research Center)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

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