Intestinal Cell News Volume 5.03 | Feb 1 2019

TOP STORY

Interleukin-22 Protects Intestinal Stem Cells against Genotoxic Stress

Scientists demonstrated that interleukin-22 (IL-22) was required for effective initiation of the DNA damage response (DDR) following DNA damage. Stem cells deprived of IL-22 signals and exposed to carcinogens escaped DDR-controlled apoptosis, contained more mutations and were more likely to give rise to colon cancer. [Nature] Abstract | Press Release

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Identification of Enteroendocrine Regulators by Real-Time Single-Cell Differentiation Mapping

The time-resolved map of transcriptional changes predicted multiple novel molecular regulators. Nine of these were validated by conditional knockout in mice or CRISPR modification in intestinal organoids. Six novel candidate regulators yielded specific enteroendocrine phenotypes. [Cell] Abstract | Press Release | Graphical Abstract

Vasoactive Intestinal Peptide Controls the Suprachiasmatic Circadian Clock Network via ERK1/2 and DUSP4 Signaling

Researchers showed that suprachiasmatic nucleus slices in organotypic culture demonstrated rapid and sustained circuit-level circadian responses to vasoactive intestinal peptide (VIP) that were mediated at a cell-autonomous level. Signaling via ERK1/2 and tuning by its negative regulator DUSP4 were critical elements of the VIP-directed circadian re-programming. [Nat Commun] Full Article

VPAC1 Couples with TRPV4 Channel to Promote Calcium-Dependent Gastric Cancer Progression via a Novel Autocrine Mechanism

VPAC1 activation by vasoactive intestinal peptide markedly induced TRPV4-mediated Ca²⁺ entry, and eventually promoted gastric cancer progression in a Ca²⁺ signaling-dependent manner. Inhibition of VPAC1 and its signaling pathway could block the progressive responses. [Oncogene] Abstract

NF-κB-Induced NOX1 Activation Promotes Gastric Tumorigenesis through the Expansion of SOX2-Positive Epithelial Cells

In situ hybridization indicated that NADPH oxidase 1 (NOX1) mRNA was detected in proliferating cells of gastritis and gastric tumors, and pharmacological inhibition of NOX activity significantly suppressed the proliferation of MKN45 gastric cancer cells and gastric hyperplasia of K19-C2mE mice. [Oncogene] Full Article

Bmi1 Marks Gastric Stem Cells Located in the Isthmus in Mice

In gastric organoids, Bmi1-expressing cells provided progeny. Ablation of Bmi1-expressing cells resulted in impaired gastric epithelium in both the mouse stomach and organoids. [J Pathol] Abstract

CK2 Inhibition with Silmitasertib Promotes Methuosis-Like Cell Death Associated to Catastrophic Massive Vacuolization of Colorectal Cancer Cells

The authors showed that inhibition of CK2 with silmitasertib decreased in vitro tumorigenesis of colorectal cancer cells in response to G2/M arrest, which correlated with mTORC1 inhibition and formation of large cytoplasmic vacuoles. Notably, molecular markers indicated that these vacuoles derive from massive macropinocytosis. [Cell Death Dis] Full Article

miR-22 and miR-214 Targeting BCL9L Inhibit Proliferation, Metastasis, and Epithelial-Mesenchymal Transition by Down-Regulating Wnt Signaling in Colon Cancer

After transfection with miR-22 expression vector, the cell proliferation and migration capacity of HCT116 and RKO cells were significantly suppressed. Also, E-cadherin was increased and vimentin was decreased by miR-22 overexpression. Similar effects were also observed after miR-214 expression vector transfection. [FASEB J] Abstract

Differential Anti-Tumor Effects of MTH1 Inhibitors in Patient-Derived 3D Colorectal Cancer Cultures

Hypoxia and reoxygenation – conditions that increase intracellular reactive oxygen species (ROS) levels – increased sensitivity to (S)-crizotinib, but not to TH588. (S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds. [Sci Rep] Full Article

Synergistic Activation of the NEU4 Promoter by p73 and AP2 in Colon Cancer Cells

Under serum starvation, NEU4 was up-regulated and one of the NEU4 target glycans, sialyl Lewis X, was decreased, whereas p73 and AP2 were up-regulated. Sialyl Lewis X levels were not, however, decreased under starvation conditions in p73- or AP2-knockdown cells. [Sci Rep] Full Article

Indispensable Role of the Ubiquitin-Fold Modifier 1-Specific E3 Ligase in Maintaining Intestinal Homeostasis and Controlling Gut Inflammation

At the cellular and molecular levels, Ufbp1 deficiency caused elevation of endoplasmic reticulum stress and activation of the unfolded protein response and cell death program. Administration of a small molecular chaperone partially prevented loss of Paneth cells caused by acute Ufbp1 deletion. [Cell Discov] Full Article

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Escherichia coli Pathobionts Associated with Inflammatory Bowel Disease

Results from studies of both cell cultures and animal models reveal pathogenic features of E. coli pathobionts, which may link them to IBD pathogenesis. This suggests that IBD-associated E. coli strains play a facilitative role during IBD flares. In this review, the authors explain IBD-associated E. coli and its role in IBD pathogenesis. [Clin Microbiol Rev] Abstract

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

Trovagene and PoC Capital Enter Agreement to Fund Clinical Development of Onvansertib in Metastatic Colorectal Cancer (mCRC)

Trovagene, Inc. announced an agreement with PoC Capital, LLC, to fund clinical development of onvansertib, Trovagene’s first-in-class, 3^rd generation oral and highly selective polo-like kinase 1 inhibitor in a Phase Ib/II clinical trial in patients with mCRC. [Trovagene, Inc.] Press Release

Genetic Immunity Expands JSC Pharmadis Partnership by Granting 20 Cancer Vaccine Licenses for Russia and Commonwealth of Independent States

Genetic Immunity announced that it is expanding its collaboration with JSC Pharmadis by granting licenses to twenty cancer indications of its trans-dermally delivered pDNA-based vaccine technology. [Genetic Immunity (PR Newswire Association LLC.)] Press Release

NMPA Accepts New Drug Application for IBI-305, a Biosimilar Product Candidate of Bevacizumab (Avastin^®)

Innovent Biologics, Inc. announced that the National Medical Products Administration (NMPA) has accepted its new drug application for a biosimilar product candidate of bevacizumab. [Innovent Biologics, Inc.] Press Release

Dr. Caroline Lindemans explains her work on intestinal repair following injury in graft versus host disease. Listen Now

Macedonia Name Change Paves Way for Science Cooperation with Greece

A political agreement between Greece and its smaller northern neighbor, the Republic of Macedonia, ends a longstanding dispute over the republic’s name and sets the stage for renewed cross-border collaboration in research and higher education. [Nature News] Editorial

A 25% Pay Raise? That’s Not Nearly Enough, Young Indian Scientists Say

In response to months of protests and marches, the Indian government announced yesterday that it will give early-career scientists raises of up to 25%. But leaders of the protest movement, who had asked for an 80% hike, immediately rejected the offer. [ScienceInsider] Editorial

NEW Nature Conference on Cellular Metabolism
April 8-11, 2019
Xiamen, China

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NEW Research Associate – Infections, Inflammation & Colorectal Cancer (Imperial College of London)

PhD Student – Biopharmaceutical Drug Delivery (Technical University of Denmark)

Research Assistant – Stem Cell Biology of the Intestine (Cancer Research UK Cambridge Institute)

Postdoctoral Position – Colon Cancer (Vanderbilt University)

Postdoctoral Research Opportunities – Cancer Center Program (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Fellow – Intestinal Stem Cell & Cancer (Francis Crick Institute)

Postdoctoral Fellow – Intestinal Immune System (Washington University School of Medicine, St.Louis)

Research Scientist – Intestinal Biology (Evotec AG)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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