Intestinal Cell News Volume 6.41 | Oct 23 2020

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    2020-08-23 | ICN 6.41


    Intestinal Cell News by STEMCELL Technologies
    Vol. 6.41 – 23 October, 2020
    TOP STORY

    Single-Cell
    Multiomics Sequencing Reveals Prevalent Genomic Alterations in Tumor Stromal Cells of Human Colorectal Cancer

    To dissect alterations in non-malignant cells, researchers performed single-cell multiomics sequencing of 21 patients with microsatellite-stable CRCs and six cancer-free, elderly individuals.
    [Cancer Cell]

    AbstractGraphical Abstract


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    PUBLICATIONSRanked by the impact factor of the journal

    5-FU
    Promotes Stemness of Colorectal Cancer via p53-Mediated WNT/β-Catenin Pathway Activation

    Researchers indicated p53 as a critical mediator of 5-Fluorouracil (5-FU)-induced cancer stem cell activation via the WNT/β-catenin signaling pathway and highlighted the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for colorectal cancer patients.
    [Nature Communications]

    Full Article

    Extracellular
    Cyclic Dinucleotides Induce Polarized Responses in Barrier Epithelial Cells by Adenosine Signaling

    Scientists found that cyclic dinucleotides (CDNs) containing adenosine induced a robust CFTR-mediated chloride secretory response together with cAMP-mediated inhibition of Poly I:C-stimulated IFNβ expression. Signal transduction was strictly polarized to the serosal side of the epithelium, dependent on the extracellular and sequential hydrolysis of CDNs to adenosine by the ectonucleosidases ENPP1 and CD73, and occurred via activation of A2B adenosine receptors.
    [Proceedings of the National Academy of Sciences of the United States of America]

    Full Article

    The
    Fragile X Mental Retardation Protein Regulates RIP1K and Colorectal Cancer Resistance to Necroptosis

    Investigators used a well-established mouse model of sporadic colorectal cancer induced by azoxymethane to determine the possible role of fragile X mental retardation protein in colorectal cancer.
    [Cellular and Molecular Gastroenterology and Hepatology]

    Full Article

    Molecular
    Mechanisms of Calcium‐Mediated Small Intestinal Glucose and Sodium Absorption through the CICR and the SOCE

    Glucose absorption and channel expression were examined in mouse upper jejunal epithelium by Ussing chamber study and immunocytochemistry, respectively. Ca2+ and Na+ imaging was also performed in single intestinal epithelial cells.
    [British Journal of Pharmacology]

    Abstract

    M2
    Macrophage-Derived Exosomal-miR-590-3p Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via the LATS1/YAP/β-Catenin Signalling Axis

    M2 macrophage-derived exosomal miR-590-3p reduced inflammatory signals and promoted epithelial regeneration by targeting LATS1 and subsequently activating YAP/β-catenin-regulated transcription
    [Journal of Crohns & Colitis]

    Abstract

    APC Loss Induces Warburg Effect via Increased PKM2
    Transcription in Colorectal Cancer

    The effects of APC-loss or Wnt ligand on the identified enzymes, PKM2 and LDHA, as well as Warburg effects were investigated. A linkage between activation of Wnt/β-catenin signaling and cancer metabolism was analysed in tumor of Apcmin/+ mice and CRC patients. The roles of PKM2 in cancer metabolism, which depended on Wnt/β-catenin signaling, were assessed in xenograft-tumors.
    [British Journal of Cancer]

    Abstract

    Identification
    of BCL-XL as Highly Active Survival Factor and Promising Therapeutic Target in Colorectal Cancer

    By RNA sequencing analysis of a pan-cancer cohort comprising >1500 patients and subsequent prediction of protein activity, BCL-XL was identified as the only antiapoptotic BCL-2 protein that was overactivated in colorectal cancer.
    [Cell Death & Disease]

    Full Article

    IL-8/CXCR2
    Mediates Tropism of Human Bone Marrow-Derived Mesenchymal Stem Cells toward CD133+/CD44+ Colon Cancer Stem Cells

    Low concentration of IL‐8 peptide inhibitors (100 ng/ml) and CXC receptor 2 (CXCR2) inhibitors had little effect on the migration of bone marrow‐derived MSCs, but could effectively weaken colon cancer stem cell stemness (CSCs) and promoted dormant CSCs in the coculture system to re‐enter into the cell cycle.
    [Journal of Cellular Physiology]

    Abstract


    Immunofluorescence image of adult stem cell-derived intestinal organoids.
    REVIEWS

    Roles
    of Src Family Kinase, Ras, and mTOR Signaling in Intestinal Epithelial Homeostasis and Tumorigenesis

    Dysregulation of intestinal epithelial cells (IEC) homeostasis likely contributes to the development of intestinal inflammation and intestinal cancer. The roles of receptor protein tyrosine kinases and their downstream signaling molecules such as Src family kinases, Ras, and mammalian target of rapamycin in homeostatic regulation of IEC turnover have recently been evaluated.
    [Cancer Science]

    Abstract

    INDUSTRY AND POLICY NEWS

    NeuClone
    Announces Positive Results from Phase I Study of Stelara® (Ustekinumab) Biosimilar Candidate

    NeuClone Pharmaceuticals Ltd announced its biosimilar candidate of Stelara®, NeuLara, has successfully met all primary and secondary endpoints in a Phase I clinical trial. NeuLara is being developed as a biosimilar of ustekinumab, an antibody targeting interleukin-12 and -23, approved under the brand name Stelara® to treat patients with plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis.
    [NeuClone Pharmaceuticals Ltd.]

    Press Release

    FEATURED EVENT

    The
    Evolving Tumor Microenvironment In Cancer Progression: Mechanisms And Emerging Therapeutic Opportunities

    January 9 – January 12, 2021
    Lake Buena Vista, Florida, United States


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    JOB OPPORTUNITIES

    Postdoctoral Research Associate – Colorectal Cancer

    The University of Utah – Salt Lake City, UT, United States

    Postdoctoral Associate – Microbiome Analytics

    University of Minnesota – Minneapolis, Minnesota, United States

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    Research Technologist – Inflammation and immunity

    Lerner Research Institute – Cleveland, Ohio, United States

    Research Associate – Ex
    Vivo     and In Vivo models of Colorectal Cancer

    Moffitt Cancer Center – Tempa, Florida, United States

    Postdoctoral
    Associate – The Relationship between Diet, Metabolism, Microbiome, and Colorectal Cancer

    Baylor College of Medicine – Houston, Texas, United States

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