Intestinal Cell News Volume 2.10 | Mar 18 2016

The Pro-Survival IKK-Related Kinase IKKepsilon Integrates LPS and IL-17A Signaling Cascades to Promote Wnt-Dependent Tumor Development in the Intestine
Researchers assessed the relationship between the pro-inflammatory Ikk-related kinase, Ikkepsilon, in Wnt-driven tumor development. They found that Ikkepsilon was activated in intestinal tumors forming upon loss of the tumor suppressor Apc. [Cancer Res] Abstract

NLRX1 Acts as an Epithelial-Intrinsic Tumor Suppressor through the Modulation of TNF-Mediated Proliferation
Investigators identified NLRX1 as a suppressor of colonic tumorigenesis that acts by controlling epithelial proliferation in the intestine during the regeneration phase following mucosal injury. [Cell Rep]
Full Article | Graphical Abstract

Dual Targeting of Bromodomain and Extra-Terminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells
Researchers demonstrated that bromo and extra-terminal domain inhibitors (BETi) downregulate c-MYC expression and inhibit colorectal cancer cell proliferation, and identified strategies for enhancing the effects of BETi on c-MYC repression by combinatorial targeting the c-MYC super-enhancer. [Mol Cancer Ther] Abstract

Gankyrin Activates mTORC1 Signaling by Accelerating TSC2 Degradation in Colorectal Cancer
Scientists report that gankyrin promotes the initiation and development of colorectal carcinogenesis by activating mTORC1 signaling, through TSC/Rheb dependent mechanism. [Cancer Lett] Abstract

Identification of a Novel Interaction between Corticotropin Releasing Hormone (Crh) and Macroautophagy
Investigators report a functional interaction between macroautophagy and Crh in the gut. They uncovered sustained basal autophagy in the gut of Crh^−/− mice, which persisted over the course of DSS administration. [Sci Rep] Full Article

Transcriptional Activation of FN1 and IL11 by HMGA2 Promotes the Malignant Behavior of Colorectal Cancer
Researchers showed that ectopic expression of HMGA2 significantly enhanced cell migration and invasion in vitro and promoted tumor growth and distant metastasis in vivo. [Carcinogenesis] Abstract

Kinase-Dependent and Independent Roles for PTK6 in Colon Cancer
To further explore functions of protein tyrosine kinase 6 (PTK6) in colon cancer, expression of epithelial and mesenchymal markers, as well as proliferation, migration, and xenograft tumor growth were examined in human colon tumor cell lines with knockdown or overexpression of PTK6 [Mol Cancer Res] Abstract

The Cryptosporidium parvum C-type lectin CpClec Mediates Infection of Intestinal Epithelial Cells via Interactions with Sulfated Proteoglycans
The authors evaluated the mechanisms underlying interactions of CpClec with intestinal epithelial cells using an Fc-tagged recombinant protein. CpClec-Fc displayed Ca²⁺-dependent, saturable binding to HCT-8 and Caco-2 cells, and competitively inhibited C. parvum attachment to and infection of HCT-8 cells. [Infect Immun] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development
The authors hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations. Manipulating VEGF bioavailability led to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. [PLoS One] Full Article

Modeling of Drug-Mediated CYP3A4 Induction by Using Human iPS Cell-Derived Enterocyte-Like Cells
Scientists overlaid Matrigel on human induced pluripotent stem cells-derived enterocyte-like cells (hiPS-ELCs) to generate the mature hiPS-ELCs that could be applied to drug-mediated CYP3A4 induction test. [Biochem Biophys Res Commun] Full Article

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Children’s Hospital Los Angeles Awarded $7.1 Million By CIRM
Tracy C. Grikscheit, MD, of The Saban Research Institute of Children’s Hospital Los Angeles has received a $7.1 million grant from the California Institute of Regenerative Medicine Translational Research program to develop a cellular therapy for the treatment of nerve disorders of the digestive system. [Children’s Hospital Los Angeles] Press Release

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Postdoctoral Position or Research Scientist – Mucosal Immunology (Qu Biologics)

Postdoctoral Training Fellow – Intestinal Tissue Engineering (The Francis Crick Institute)

Postdoctoral Researcher – Mechanisms of Intestinal Persistence (Institute of Food Research)

Program Director – IBD and Crohn’s Disease Program (The Leona M. and Harry B. Helmsley Charitable Trust)

Faculty Position – Cancer Research (Texas Tech University)

Postdoctoral Fellow – Nanomedicine (Johns Hopkins University)

Faculty Position – Cancer Research (Texas Tech University Health Sciences Center)

Postdoctoral Position – Tumor Immunology (Medical University of South Carolina)

Postdoctoral Fellowship – Immunology (Beth Israel Deaconess Medical Center)

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