Intestinal Cell News Volume 3.19 | May 26 2017

TOP STORY

Stromal-Derived IGF2 Promotes Colon Cancer Progression via Paracrine and Autocrine Mechanisms

Researchers showed that insulin-like growth factor (IGF)2 was specifically induced in the tumor stroma of colorectal cancer (CRC) and identified cancer-associated fibroblasts as the major source. They provided functional evidence that stromal IGF2, via the paracrine IGF1 receptor/insulin receptor axis, activated pro-survival AKT signaling in CRC cell lines. [Oncogene] Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Human MSCs Promotes Colorectal Cancer Epithelial–Mesenchymal Transition and Progression via CCL5/β-Catenin/Slug Pathway

The authors aimed to identify the role of inflammation-activated-mesenchymal stem cells (MSCs) in colorectal cancer development. Their results showed that tumor necrosis factor-α-preactivated-human MSCs significantly promote the progression of colon cancer cells by enhancing cell proliferation, epithelial–mesenchymal transition, migration, and invasion. [Cell Death Dis] Full Article

PAK4 Regulates G6PD Activity by p53 Degradation Involving Colon Cancer Cell Growth

Investigators reported that p21-activated kinase 4 (PAK4) promoted glucose intake, NADPH production and lipid biosynthesis, leading to an increased proliferation of colon cancer cells. Mechanistically, PAK4 interacted with glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway and increased G6PD activity via enhancing Mdm2-mediated p53 ubiquitination degradation. [Cell Death Dis] Full Article

HpSlyD Inducing CDX2 and VIL1 Expression Mediated through TCTP Protein May Contribute to Intestinal Metaplasia in the Stomach

To investigate the signaling pathway involved in HpSlyD-induced intestinal metaplasia, CDX2 and VIL1 expressions were determined before and after HpSlyD application. The results showed HpSlyD induced CDX2 and VIL1 expressions. TCTP protein expression was markedly increased after application of HpSlyD and in an HpSlyD-expressing stable cell line. [Sci Rep] Full Article

miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2

The authors first used laser capture microdissection to obtain purified cells from four deficient mismatch repair (dMMR) and four proficient mismatch repair colon cancer tissues. Second, microRNA (miRNA) microarray chips were used to identify miRNAs that are differentially expressed between these two classes of tumors. Third, they analyzed their differential expression by qRT-PCR in a panel of 5-fluorouracil (5-FU)-resistant colon cancer cell lines. They identified that miR-1290 was one of the most upregulated miRNAs in both dMMR colon cancer tissues and 5-FU-resistant cells. [Mol Ther Nucleic Acids] Full Article

Downregulation of miR-199a/B-5p Is Associated with GCNT2 Induction upon Epithelial–Mesenchymal Transition in Colon Cancer

The results indicated that GCNT2 is upregulated upon epithelial–mesenchymal transition induced with EGF and basic FGF in cultured human colon cancer cells. GCNT2 knockdown or overexpression decreased or increased, respectively, malignancy-related characteristics of colon cancer cells and I antigen levels. [FEBS Lett] Abstract

Resveratrol Inactivates PI3K/Akt Signaling through Upregulating BMP7 in Human Colon Cancer Cells

Scientists investigated the anticancer activity of resveratrol (Res) in human colon cancer cells, and unveiled the possible mechanism for this effect. With cell viability, flow cytometry, PCR and western blot analysis, they demonstrated the efficacious anticancer activity of Res in HCT116 cells. Mechanically, they found that Res greatly upregulates BMP7 in HCT116 cells. [Oncol Rep] Abstract

A Novel SIRT1 Inhibitor, 4bb Induces Apoptosis in HCT116 Human Colon Carcinoma Cells Partially by Activating p53

Researchers report the discovery of a novel quinoxaline based small molecule inhibitor of human SIRT1, 4bb. They investigated its effect on viability of colon cancer cells, and molecular mechanism of action. In vitro, 4bb is a significantly more potent SIRT1 inhibitor, compared to β-naphthols such as sirtinol, cambinol. [Biochem Biophys Res Commun] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Organoid-Based Epithelial to Mesenchymal Transition (OEMT) Model: From an Intestinal Fibrosis Perspective

Scientists generated an OEMT model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice. Transforming growth factor- β1 alone slightly induced epithelial to mesenchymal transition in the IEOs but mainly disrupted them. [Sci Rep] Full Article

Primary Human Polarized Small Intestinal Epithelial Barriers Respond Differently to a Hazardous and an Innocuous Protein

In vitro indicators of monolayer integrity, cytotoxicity, and inflammation were evaluated using primary human polarized small intestinal epithelial barriers cultured on Transwell^® filters to compare effects of a hazardous protein (Clostridium difficile Toxin A [ToxA]) and an innocuous protein (bovine serum albumin). ToxA exerted a reproducible decrease on barrier integrity at doses comparable to those producing effects observed from cell line-derived intestinal epithelial cell monolayers, with transepithelial electrical resistance being the most sensitive indicator. [Food Chem Toxicol] Full Article

Roles of Intestinal Epithelial Cells in the Maintenance of Gut Homeostasis

Intestinal epithelial cells greatly contribute to the maintenance of the symbiotic relationship between gut microbiota and the host by constructing mucosal barriers, secreting various immunological mediators and delivering bacterial antigens. Impairment of the innate immune functions of intestinal epithelial cells is associated with intestinal inflammation. [Exp Mol Med] Full Article

Molecular Basis of Alcohol-Related Gastric and Colon Cancer

Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of β-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. [Int J Mol Sci] Full Article

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FDA Approves Merck’s KEYTRUDA^® (Pembrolizumab) for Adult and Pediatric Patients with Unresectable or Metastatic, Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient Cancer

Merck announced that the U.S. Food and Drug Administration (FDA) has approved a new indication for KEYTRUDA^®, the company’s anti-PD-1 therapy. KEYTRUDA is now indicated for the treatment of adult and pediatric patients with unresectable or metastatic, MSI-H or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. [Merck & Co., Inc.] Press Release | Editorial

Investing in Innovation

Massachusetts Life Sciences Center (MLSC) gives Boston biomedicine an $18 million boost. Four new projects, each run by Boston-based members of the Harvard biomedical research community, are funded by the new capital infrastructure grants from the MLSC. [Harvard Medical School] Press Release

How NSF Cut 11% from Its Budget

Last fall’s divisive presidential campaign was still underway when Jim Olds, who leads the biology directorate at the National Science Foundation (NSF) in Arlington, Virginia, began worrying that the agency could soon be facing a serious budget crunch. It was already under a government-wide spending freeze, and Olds wanted to be prepared if things got worse. So he asked his staff to begin thinking about how to handle a 20% cut in the directorate’s $724 million budget. That hypothetical exercise turned into an ugly reality this spring when NSF learned that the winner of that election, Donald Trump, planned to include an 11% cut to NSF’s $7.4 billion budget in his first full spending request to Congress. [ScienceInsider] Editorial

Monument to Peer Review Unveiled in Moscow

A good-humored crowd of more than 100 people — including students, researchers and Russia’s deputy minister of education and science — gathered outside Moscow’s Higher School of Economics to witness the unveiling of what is probably the world’s first monument to peer review. [Nature News] Editorial

Colombian Biologist Cleared of Criminal Charges for Posting Another Scientist’s Thesis Online

A Colombian biologist who faced a criminal trial for posting another scientist’s thesis online has been cleared of copyright violation — an offense that, under Colombian law, might have brought him a jail sentence. [Nature News] Editorial

NEW Gordon Research Conferences: Cell Growth & Proliferation
July 9-14, 2017
Mount Snow, United States

NEW The TGF-β Superfamily: Signaling in Development and Disease
July 9-14, 2017
Lisbon, Portugal

NEW Intestinal Organoid Virtual Training
October 17-25, 2017
Online

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NEW Postdoctoral Fellowships – Epithelial Cell Biology & Gastrointestinal Neoplasia (Vanderbilt University Medical Center)

PhD Studentship – Human Intestinal Epithelial Cell Biology (University of Cambridge)

Postdoctoral Fellow – Medical Biochemistry and Mucin Biology (University of Gothenburg)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

Postdoctoral Research Fellow – Inflammatory Bowel Disease (Children’s Hospital Los Angeles)

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

PhD Position – Colorectal Cancer (German Cancer Research Center/DKFZ)

Postdoctoral Fellow – Nanomedicine (Johns Hopkins University)

Postdoctoral and PhD Positions – Bio-Nano Science (University of South Australia)

Postdoctoral Fellow Position – Cancer Biology (Emory University)

Assistant or Associate Member – Stem Cell/Gene Therapy (Fred Hutchinson Cancer Research Center)

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