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The cell polarity protein Scrib functions as a tumor suppressor in liver cancer

  1. Author:
    Kapil, Shweta
    Sharma, Bal Krishan
    Patil, Mallikarjun
    Elattar, Sawsan
    Yuan, Jinling
    Hou, Steven
    Kolhe, Ravindra
    Satyanarayana, Ande

  2. Author Address

    Department of Biochemistry and Molecular Biology, Molecular Oncology & Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA., Stem Cell Regulation and Animal Aging Section, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Department of Pathology, Augusta University, Augusta, GA 30912, USA.,
    1. Year: 2017
    2. Date: Apr 18
  2. Journal: Oncotarget
    1. 8
    2. 16
    3. Pages: 26515-26531
  4. Type of Article: Article
  1. Abstract:

    Scrib is a membrane protein that is involved in the maintenance of apical-basal cell polarity of the epithelial tissues. However, Scrib has also been shown to be mislocalized to the cytoplasm in breast and prostate cancer. Here, for the first time, we report that Scrib not only translocates to the cytoplasm but also to the nucleus in hepatocellular carcinoma (HCC) cells, and in mouse and human liver tumor samples. We demonstrate that Scrib overexpression suppresses the growth of HCC cells in vitro, and Scrib deficiency enhances liver tumor growth in vivo. At the molecular level, we have identified the existence of a positive feed-back loop between Yap1 and c-Myc in HCC cells, which Scrib disrupts by simultaneously regulating the MAPK/ERK and Hippo signaling pathways. Overall, Scrib inhibits liver cancer cell proliferation by suppressing the expression of three oncogenes, Yap1, c-Myc and cyclin D1, thereby functioning as a tumor suppressor in liver cancer.

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External Sources

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  2. DOI: 10.18632/oncotarget.15713
  3. PMID: 28460446
  4. View record in Web of Science®
  5. WOS: 000399819700060

Library Notes

  1. Fiscal Year: FY2016-2017
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