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

Shweta Kapil, Bal Krishan Sharma, Mallikarjun Patil, Sawsan Elattar, Jinling Yuan, Steven X. Hou, Ravindra Bharat Kolhe, Satyanarayana Ande

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)26515-26531
Number of pages17
JournalOncotarget
Volume8
Issue number16
DOIs
StatePublished - Jan 1 2017

Keywords

  • ERK
  • HCC
  • Hippo signaling
  • Nuclear localization
  • Yap1

ASJC Scopus subject areas

  • Oncology

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