Intestinal Cell News Volume 3.26 | Jul 14 2017

TOP STORY

Chromosome Rearrangements Drive Formation and Growth of Colorectal Cancer

Genetic mutations caused by rearranged chromosomes drive the development and growth of certain colorectal cancers, according to new research. Investigators describe how large pieces of chromosomes are deleted or inverted, resulting in new, mutated so-called fusion genes created from parts of two other genes that are responsible for the formation of some colon cancers. [Press release from Weill Cornell Medicine discussing online prepublication in Nature Communications] Press Release | Full Article

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Blocking Endothelin-1-Receptor/β-Catenin Circuit Sensitizes to Chemotherapy in Colorectal Cancer

Scientists showed the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1, which initiates signaling cascades as part of the signaling complex. [Cell Death Differ] Full Article

Disrupting G6PD-Mediated Redox Homeostasis Enhances Chemosensitivity in Colorectal Cancer

Scientists investigated the potential roles of glucose-6-phosphate dehydrogenase (G6PD) in colorectal cancer (CRC) development and chemoresistance. They discovered that G6PD is overexpressed in CRC cells and patient specimens. [Oncogene] Full Article

Pyruvate Dehydrogenase Kinase 4 Exhibits a Novel Role in the Activation of Mutant KRAS, Regulating Cell Growth in Lung and Colorectal Tumor Cells

Using isogenic cells and a panel of colorectal and lung cell lines, researchers demonstrated that KRAS mutant cells showed a dependency on PDHK4 whereas KRAS wild-type cells were significantly resistant to PDHK4 knockdown. They found that PDHK4 plays a role in the post-translational regulation of mutant KRAS activity. [Oncogene] Full Article

Streptococcus gallolyticus subsp. gallolyticus Promotes Colorectal Tumor Development

Investigators demonstrated that Streptococcus gallolyticus subsp. gallolyticus (Sg) promotes human colon cancer cell proliferation in a manner that depends on cell context, bacterial growth phase and direct contact between bacteria and colon cancer cells. In addition, they observed increased level of β-catenin, c-Myc and PCNA in colon cancer cells following incubation with Sg. [PLoS Pathog] Full Article

Colorectal Cancer Stem Cells Acquire Chemoresistance through the Upregulation of FBXW7 and the Consequent Degradation of c-Myc

Researchers elucidated the molecular mechanisms responsible for evading cell death in colorectal cancer stem cells (CSCs) mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, they found that c-Myc expression was substantially decreased in colorectal CSCs. [Stem Cells] Abstract

The Essential Role of TAp73 in Bortezomib-Induced Apoptosis in p53-Deficient Colorectal Cancer Cells

Investigators evaluated the toxicity of bortezomib in the colorectal cancer (CRC) cell lines HCT116 wild-type and its p53^−/− clone. Transient resistance to bortezomib treatment was observed in p53-null cells that was later accompanied by an increase in levels and nuclear translocation of TAp73, an isoform of the p53-homologue p73, as well as induction of apoptosis. [Sci Rep] Full Article

Expression of Protein Kinase C Gamma Promotes Cell Migration in Colon Cancer

The authors demonstrated that a reduction in the levels of protein kinase C (PKC) gamma in the colon cancer cells inhibits cell migration and foci formation. They observed an increase in cell adhesion and proliferation following the reduction of PKC gamma levels in the cell. [Oncotarget] Full Article

MDR1A Deficiency Restrains Tumor Growth in Murine Colitis-Associated Carcinogenesis

Investigators found that protein expression of ATP binding cassette subfamily B member 1 (ABCB1)/multidrug resistance 1 (MDR1) was diminished in the intestinal mucosa of patients with active ulcerative colitis (UC) with or without colorectal cancer (CAC), but not in non-UC patients with sporadic colon cancer. They investigated the consequences of ABCB1/MDR1 loss-of-function in a common murine model for CAC. [PLoS One] Full Article

Exposure to Anisakis Extracts Can Induce Inflammation on In Vitro Cultured Human Colonic Cells

Scientists investigated if crude extracts obtained from Anisakis larvae marinated in a solution with added allyl isothiocyanate and frozen, or from frozen only Anisakis larvae, can induce an inflammatory effect on in vitro differentiated colonic Caco-2 cells exposed or not to LPS. [Parasitol Res] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Endothelial Hey2 Deletion Reduces Endothelial-to-Mesenchymal Transition and Mitigates Radiation Proctitis in Mice

Total body irradiation and radiation proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, endothelial-to-mesenchymal transition (EndoMT) and rectal damage severity. Researchers found that EndoMT occurs in irradiated human umbilical vein endothelial cells with concomitant Hey2 mRNA and protein increase. [Sci Rep] Full Article

The Extracellular Matrix of the Gastrointestinal Tract: A Regenerative Medicine Platform

The authors discuss the importance of tissue-specific extracellular matrix bioscaffolds and highlight the major advances that have been made in regenerative medicine strategies for the reconstruction of functional gastrointestinal tissues. [Nat Rev Gastroenterol Hepatol] Abstract

Dclk1-Expressing Tuft Cells: Critical Modulators of the Intestinal Niche?

Scientists outline and discuss emerging evidence that strongly supports tuft cells as key regulatory cells in the complex network of the intestinal microenvironment. [Am J Physiol Gastrointest Liver Physiol] Abstract

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

Daiichi Sankyo, Max Planck Innovation and Lead Discovery Center Announce Cancer Research Collaboration

Daiichi Sankyo Co., Limited, Max Planck Innovation GmbH and the Lead Discovery Center GmbH have signed an agreement providing Daiichi Sankyo with the option to receive the exclusive rights to a new lead compound for the treatment of cancer to be discovered and developed at the Lead Discovery Center. [Daiichi Sankyo Co., Limited] Press Release

MMC and Partnering Institutions Awarded $20M by the NIH

The National Institutes of Health (NIH) has announced a five-year, $20 million research grant to Maine Medical Center (MMC), its research institute and their partnering institutions, the University of Vermont and the University of Southern Maine. Funding from this award will help researchers develop and implement innovative medical treatments for many chronic diseases prevalent in the region including cancer, heart disease, obesity, diabetes, Alzheimer’s disease and substance abuse. [Maine Medical Center] Press Release

Marketing of Unproven Stem Cell–Based Interventions: A Call to Action

Commercial promotion of unsupported therapeutic uses of stem cells is a global problem that has proven resistant to regulatory efforts. The authors suggest a coordinated approach at the national and international levels focused on engagement, harmonization, and enforcement to reduce the risks associated with direct-to-consumer marketing of unproven stem cell treatments. [Sci Transl Med] Abstract | Editorial

US Lawmakers Seek $1.1 Billion Boost for the NIH

The US National Institutes of Health (NIH) would see its budget rise by US$1.1 billion in 2018, to $35.2 billion, under a spending proposal released today by lawmakers in the House of Representatives. [Nature News] Editorial

In a Rare Move, FDA Reverses Course on Drug Developed by CEO with Ties to Trump

The Food and Drug Administration has changed its tune on an experimental drug for a deadly rare disease, withdrawing a request that the company developing it run another clinical trial. The unusual move comes after President Trump met with the company’s CEO — and promised to speed up what he called a “slow and burdensome” process for drug approvals. [STAT News] Editorial

White House’s Dwindling Science Office Leaves Major Research Programs in Limbo

US President Donald Trump has pledged to shrink the federal government, and he seems to be starting with science. Nearly six months after taking office, Trump has not chosen a science adviser, and the White House’s Office of Science and Technology Policy has dwindled from around 130 staff members under former president Barack Obama to 35. [Nature News] Editorial

NEW AACR-NCI-EORTC Molecular Targets & Cancer Therapeutics
October 26-30, 2017
Philadelphia, Pennsylvania, United States

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

NEW Postdoctoral Position – Intestinal Organoids (Radboud University)

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

Postdoctoral Research Associate – Cancer Research (Southern Research Institute)

Postdoctoral Position – Intestinal Epithelial Cell Biology (University of Gothenburg)

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

Postdoctoral Research Associate – Colorectal Cancer (University of Virginia)

Postdoctoral Position – Cancer Genomics and Precision Medicine (Candiolo Cancer Institute-FPO, IRCCS)

Postdoctoral Fellow – Intestinal Pathogen Research (Boston Children’s Hospital and Harvard Medical School)

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

Assistant or Associate Member – Stem Cell/Gene Therapy (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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