Intestinal Cell News Volume 4.13 | Apr 13 2018

TOP STORY

Intra-Tumor Diversification in Colorectal Cancer at the Single-Cell Level

Scientists investigated the nature and extent of intra-tumor diversification, they characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal intestinal crypts. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Tropism for Tuft Cells Determines Immune Promotion of Norovirus Pathogenesis

Researchers showed that tuft cells express CD300lf and are the target cell for murine norovirus in the mouse intestine. [Science] Abstract | Press Release

A Selective Peptide Inhibitor of Frizzled 7 Receptors Disrupts Intestinal Stem Cells

Investigators report the identification of a potent peptide that selectively binds to the frizzled 7 receptor (FZD7) cysteine-rich domain (CRD) at a previously uncharacterized site and alters the conformation of the CRD and the architecture of its lipid-binding groove. Treatment with the FZD7-binding peptide impaired Wnt signaling in cultured cells and stem cell function in intestinal organoids. [Nat Chem Biol] Abstract

PARP-1 Protects against Colorectal Tumor Induction, but Promotes Inflammation-Driven Colorectal Tumor Progression

Using transgenic mouse models, researchers showed that poly(ADP-ribose) polymerase-1 (PARP-1) fosters inflammation-driven colorectal tumor growth and stimulates the IL6-STAT3-cyclin D1 axis in tumors. [Proc Natl Acad Sci USA] Abstract

Zinc Finger Protein 746 Promotes Colorectal Cancer Progression via C-Myc Stability Mediated by Glycogen Synthase Kinase 3β and F-Box and WD Repeat Domain-Containing 7

Zinc finger protein 746 was overexpressed in HCT116, SW620, and SW480 cells, which was supported by colorectal cancer tissue microarray and TCGA analysis. [Oncogene] Abstract

The Nuclear Translocation of the Kinases p38 and JNK Promotes Inflammation-Induced Cancer

The authors identified the importin-binding region in p38 and JNK and developed a myristoylated peptide targeting this site that they called PERY. The PERY peptide substantially inhibited inflammation in mice, as manifested in models of colitis and colitis-associated colon cancer. [Sci Signal] Full Article

PKCα in Colon Cancer Cells Promotes M1 Macrophage Polarization via MKK3/6‐P38 MAPK Pathway

Scientists showed that high PKCα expression in human colon cancer tissues correlated with better prognosis and high M1 macrophage content. PKCα expressed in colon cancer cells inhibited the growth of colon cancer in mice model. [Mol Carcinog] Abstract

Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose‐Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model

Administration of iPSC‐derived MSC stimulated significant intestinal epithelial cell proliferation, increased in the numbers of Lgr5⁺ intestinal stem cells, and increased intestinal angiogenesis. [Stem Cells Transl Med] Abstract

Regulation of Intestinal Epithelial Barrier Function by lncRNA Uc.173 through Interaction with miR-29b

Investigators report that the T-UCR uc.173 enhances the intestinal epithelial barrier function by antagonizing miR-29b. Decreasing the levels of uc.173 by gene silencing led to dysfunction of the intestinal epithelial barrier in cultured cells and increased the vulnerability of the gut barrier to septic stress in mice. [Mol Cell Biol] Abstract

Identification of G2/M Phase Transition by Sequential Nuclear and Cytoplasmic Changes and Molecular Markers in Mice Intestinal Epithelial Cells

Although the regulatory network of G2/M phase transition has been intensively studied in mammalian cell lines, the identification of morphological and molecular markers to identify G2/M phase transition in vivo remains elusive. Scientists found no obvious morphological changes between the S phase and G2 phase in mice intestinal epithelial cells. [Cell Cycle] Abstract

Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture

The authors investigated which inhibitor for stem cell-related signal improves the sensitivity for anti-cancer drug treatment in tumor air-liquid interface organoids. Treatment with Hedgehog signal inhibitors decreased the cell viability of organoids compared with Notch and Wnt signal inhibitors. [Int J Mol Sci] Full Article

A Novel Oncolytic Chimeric Orthopoxvirus Encoding Luciferase Enables Real-Time View of Colorectal Cancer Cell Infection

A novel oncolytic chimeric orthopoxvirus CF33-Fluc infected, replicated in, and killed colorectal cancer cells in vitro in a dose-dependent manner. Rapid tumor regression or stabilization occurred in vivo at a low dose over a short time period, regardless of the viral delivery method in the HCT-116 colorectal tumor xenograft model [Mol Ther Oncolytics] Full Article

Lessons from the Crypt: HMGA1—Amping Up Wnt for Stem Cells and Tumor Progression

High mobility group A1 (HMGA1) chromatin remodeling proteins are enriched in aggressive cancers and stem cells, although their common function in these settings has remained elusive until now. Recent work in murine intestinal stem cells revealed a novel role for Hmga1 in enhancing self-renewal by amplifying Wnt signaling, both by inducing genes expressing Wnt agonist receptors and Wnt effectors. [Cancer Res] Full Article

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Natera to Present Successful Results from Bladder and Colon Cancer Studies

Natera will present data demonstrating the ability of Signatera^™ to monitor treatment response, detect minimal residual disease, and identify disease recurrence in bladder and colorectal cancers. [Press release from Natera discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting, Chicago] Press Release

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

Nektar Announces Dosing of First Patient in Phase I/II Clinical Study to Evaluate Combination of TLR Agonist NKTR-262 with CD122-Biased Agonist NKTR-214 in Patients with Advanced Solid Tumors

Nektar Therapeutics announced that it has initiated dosing patients in the Phase I/II REVEAL clinical study evaluating the efficacy and safety of the combination of investigational medicines NKTR-262 and NKTR-214 in the treatment of solid tumors. [Nektar Therapeutics] Press Release

UMN Receives $42.6 Million to Expand Impact on Scientific Health Research

The University of Minnesota’s Clinical and Translational Science Institute received more than $42 million in renewed National Institutes of Health funding through the National Center for Advancing Translational Sciences’ Clinical and Translational Science Award program. [The University of Minnesota] Press Release

Panel Calls for a Postdoc Tax and Other Measures to Help Biomedical Scientists Find Jobs

The U.S. Congress, federal funding agencies, universities, and other research institutions must take significant steps, such as a postdoc “tax” and a hard cap on how long postdocs can be funded by a lab head, to better usher young biomedical scientists into viable careers, a committee from the National Academies of Sciences, Engineering, and Medicine concluded in a report. [ScienceInsider] Editorial

Spain’s Biggest-Ever Science Petition Decries ‘Abandonment’ of Research

Leading Spanish scientific organizations delivered a petition signed by more than 277,000 people to the national parliament in Madrid, calling on the government to stop the “progressive abandonment of science in Spain” caused by budget cuts. The petition is the largest ever on a science-policy subject in Spain. [Nature News] Editorial

The March for Science Is Back — and Here’s What to Expect

Nature takes a look at why people are marching, how the movement has changed over time and what its future could bring. [Nature News] Editorial

India Creates Unique Tiered System to Punish Plagiarism

The Indian government has adopted its first regulations on academic plagiarism—rules that some researchers say are too lenient and others fear go too far and will be difficult to implement. [ScienceInsider] Editorial

NEW Cold Spring Harbor (CSH): Mechanisms & Models of Cancer
August 14-18, 2018
Cold Spring Harbor, New York, United States

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NEW Postdoctoral Training Fellow – Intestinal Research (The Francis Crick Institute)

Postdoctoral Position – Digestive Health (University of California, Irvine)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral Fellowship – Intestinal Cancer (University of Gothenburg)

Postdoctoral Research Fellow – Colon Cancer (Health Sciences North Research Institute)

Postdoctoral Research Fellow – Lysosomes in Neonatal Enterocytes and Their Pathologies (Northwestern University)

Director Position – Immune Intestinal Homeostasis (Institute for Basic Science)

Postdoctoral Fellow – Mucosal Immunology (Centre of Molecular Inflammation Research)

Postdoctoral Position – Molecular Biology/Signal Transduction/ Cancer/Inflammation (Universite de Liege)

Academic Positions – Inflammatory Bowel Disease (Cedars-Sinai Inflammatory Bowel and Immunobiology Research Institute)

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