Trip6 regulates p27KIP1 to promote tumorigenesis

Victor T.G. Lin, Vivian Y. Lin, Yun Ju Lai, Chen Shan Chen, Kang Liu, Weei Chin Lin, Fang Tsyr Lin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

TRIP6 is an adaptor protein that regulates cell motility and antiapoptotic signaling. Although it has been implicated in tumorigenesis, the underlying mechanism remains largely unknown. Here we provide evidence that TRIP6 promotes tumorigenesis by serving as a bridge to promote the recruitment of p27KIP1 to AKT in the cytosol. TRIP6 regulates the membrane translocation and activation of AKT and facilitates AKT-mediated recognition and phosphorylation of p27KIP1 specifically at T157, thereby promoting the cytosolic mislocalization of p27KIP1. This is required for p27KIP1 to enhance lysophosphatidic acid (LPA)-induced ovarian cancer cell migration. TRIP6 also promotes serum-induced reduction of nuclear p27KIP1 expression levels through Skp2- dependent and -independent mechanisms. Consequently, knockdown of TRIP6 in glioblastoma or ovarian cancer xenografts restores nuclear p27KIP1 expression and impairs tumor proliferation. As TRIP6 is upregulated in gliomas and its levels correlate with poor clinical outcomes in a dose-dependent manner, it may represent a novel prognostic marker and therapeutic target in gliomas.

Original languageEnglish
Pages (from-to)1394-1409
Number of pages16
JournalMolecular and Cellular Biology
Volume33
Issue number7
DOIs
Publication statusPublished - 2013 Apr 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Lin, V. T. G., Lin, V. Y., Lai, Y. J., Chen, C. S., Liu, K., Lin, W. C., & Lin, F. T. (2013). Trip6 regulates p27KIP1 to promote tumorigenesis. Molecular and Cellular Biology, 33(7), 1394-1409. https://doi.org/10.1128/MCB.01149-12