Intestinal Cell News Volume 2.46 | Dec 16 2016

TOP STORY

NLRC3 Is an Inhibitory Sensor of PI3K–mTOR Pathways in Cancer

Researchers showed that mice lacking nucleotide-binding domain and leucine-rich repeats (NLRC3) are hyper-susceptible to colitis and colorectal tumorigenesis. The effect of NLRC3 is most dominant in enterocytes, in which it suppresses activation of the mTOR signaling pathways and inhibits cellular proliferation and stem-cell-derived organoid formation. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

ARID1A Loss Impairs Enhancer-Mediated Gene Regulation and Drives Colon Cancer in Mice

Investigators demonstrated that Arid1a functions as a tumor suppressor in the mouse colon, but not the small intestine, and that invasive ARID1A-deficient adenocarcinomas resemble human colorectal cancer. These tumors lack deregulation of APC/β-catenin signaling components, which are crucial gatekeepers in common forms of intestinal cancer. They found that ARID1A normally targets SWI/SNF complexes to enhancers, where they function in coordination with transcription factors to facilitate gene activation. [Nat Genet] Abstract | Press Release

Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling

The authors revealed the mechanisms underlying the cancer-nerve partnership. They found that Dclk1⁺ tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. [Cancer Cell] Abstract | Graphical Abstract

Different In Vivo and In Vitro Transformation of Intestinal Stem Cells in Mismatch Repair Deficiency

Mutations in mismatch repair genes result in microsatellite instability (MSI) and early onset of colorectal cancer. To get mechanistic insights into the time scale, sequence and frequency of intestinal stem cell transformation, investigators quantified MSI and growth characteristics of organoids of Msh2-deficient and control mice from birth until tumor formation and related them to tissue gene expression. [Oncogene] Abstract

The DEAD Box Protein p68: A Novel Coactivator of Stat3 in Mediating Oncogenesis

Researchers report for the first time a novel mechanism of alliance between p68 and Stat3 in stimulating transcriptional activity of Stat3. They observed that the expression of p68 and Stat3 bears strong positive correlation and significant colocalization in normal and colon carcinoma patient samples. They demonstrated that p68 directly interacts with Stat3 in HEK293 cells as well as multiple colon cancer cell lines. [Oncogene] Abstract

TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation

The authors identified TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. [Cell Rep] Full Article | Graphical Abstract

Prognostic and Predictive Significance of Long Interspersed Nucleotide Element-1 Methylation in Advanced-Stage Colorectal Cancer

Scientists investigated whether tumor LINE-1 hypomethylation correlates with patient survival and with response to 5-fluorouracil/oxaliplatin chemotherapy in advanced-stage colorectal cancer. [BMC Cancer] Full Article

Somatostatin Signaling via SSTR1 Contributes to the Quiescence of Colon Cancer Stem Cells

Neuroendocrine cells (NECs) reside adjacent to colonic stem cells (SCs) in the crypt stem cell (SC) niche, but how NECs are involved in regulation of SCs is unclear. The authors investigated NECs expressing somatostatin (SST) and somatostatin receptor type 1 (SSTR1) because SST inhibits intestinal proliferation. They hypothesized SSTR1 cells maintain SCs in a quiescent state, and aberrant SST signaling contributes to SC overpopulation in colorectal cancer. [BMC Cancer] Full Article

INTESTINAL STEM CELL & ORGANOID RESEARCH

In Vitro Patterning of Pluripotent Stem Cell-Derived Intestine Recapitulates In Vivo Human Development

Researchers identified several genes that are expressed in a region-specific manner in the developing human intestine, and using human embryonic stem cell derived intestinal organoids, they demonstrated that the time of exposure to active FGF and WNT signaling controls regional identity. [Development] Abstract

Eicosanoid Receptors: Targets for the Treatment of Disrupted Intestinal Epithelial Homeostasis

The author focuses on the role of eicosanoid receptors in the maintenance of intestinal epithelium physiology through the control of proliferation/differentiation/apoptosis processes. [Eur J Pharmacol] Abstract

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

Emmaus Life Sciences, Inc. Receives Japanese Patent for Use of L-glutamine in Treatment of Diverticulosis

Emmaus announced the allowance of patent application number 2014-547181, directed to the treatment of diverticulosis, by the Japanese Patent Office. The allowance of this application follows the issuance of corresponding patents in both Australia and China. Related patent applications are currently pending in various jurisdictions around the world, including the United States, Europe, South Korea, Brazil, Russia, India, Mexico and Indonesia. [Emmaus Life Sciences, Inc.] Press Release

NCCN Guidelines^® Recommend SIR-Spheres^® Y-90 Resin Microspheres for the Treatment of Metastatic Colorectal Cancer

Sirtex Medical Limited announced that SIR-Spheres^® Y-90 resin microspheres has been included as a Category 2A recommended treatment in the latest National Comprehensive Cancer Network^® (NCCN^®) Clinical Practice Guidelines in Oncology for colon cancer and rectal cancer. [National Comprehensive Cancer Network^®] Press Release

United Kingdom Gives Green Light for Mitochondrial Replacement Technique

Authorities in the United Kingdom have given the go-ahead for mitochondrial replacement therapy, a new type of assisted reproduction that could allow some families to avoid passing on genetic disease. The technique is controversial because it combines genetic material from three people: two eggs and one sperm. The decision has been widely anticipated. It comes after years of debate and a change in the country’s laws passed by Parliament in 2015 [Science Insider] Editorial

NIH Discusses Curbing Lab Size to Fund More Midcareer Scientists

A new analysis by the National Institutes of Health in Bethesda, Maryland, reinforces previous studies showing that productivity may lag as labs get bigger. The results suggest that NIH could fund thousands more researchers without any drop-off in scientific output if it capped the total number of grants an investigator could receive, an NIH official says. [Science Insider] Editorial

NEW Keystone Symposium: Engineered Cells and Tissues as Platforms for Discovery and Therapy
March 9-12, 2017
Boston, United States

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

NEW Research Associate – Epigenetics of Human Intestinal Epithelial Cell Pathophysiology (University of Cambridge)

Assistant Professor – Gastrointestinal Health/Physiology Tenure-Track Faculty Position (University of Maryland)

Postdoctoral Research Scientist – tRNA Repertoire Influence Ribosome Function during Intestinal Differentiation and Fibroblast Activation (Medical Research Council)

Scientific Writing Associate – Literature Review/Analysis and Relevant Scientific and Medical Material (Genfit SA)

Tenure-Track Position – Various Projects (University Medical Center Utrecht)

Research Officer – Transcriptional and Epigenetic Regulation in Colon Cancer and Intestinal Development (Hudson Institute of Medical Research)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Academic Gastrointestinal Pathologist – Faculty Position (University of Utah)

Research Technician III IV – Gastrointestinal Cancer (Fred Hutchinson Cancer Research Center)

Portfolio Manager – Material and Recipe Manager (Nestle Institute of Health Sciences)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

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