Reduction of cytosolic p27Kip1 inhibits cancer cell motility, survival, and tumorigenicity

Frederick Y. Wu, Shizhen Emily Wang, Melinda E. Sanders, Incheol Shin, Federico Rojo, Jose Baselga, Carlos L. Arteaga

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

We generated a p27Kip1 mutant (p27ΔNLS) that localized exclusively in cell cytosol. Expression of p27ΔNLS in MCF7 breast cancer cells down-regulated RhoA and increased motility, survival, and Akt levels without an effect on cell cycle distribution. RNA interference of p27 in U87 glioma cells, which express p27 predominantly in the cytoplasm, inhibited motility and survival. Conversely, knockdown of p27 in COS7 cells, with >95% nuclear p27 expression, accelerated proliferation but had no effect on motility or survival. U87 cells in which p27 had been eliminated by RNA interference exhibited lower Akt levels, shorter Akt turnover, and markedly impaired tumorigenicity in vivo. These xenografts were less invasive and exhibited increased apoptosis compared with p27-expressing tumors. Expression of cytosolic p27 in primary human breast carcinomas correlated linearly with Akt content as measured by immunohistochemistry. These data suggest that cytoplasmic p27 can exert oncogenic functions by modulating Akt stability, cell survival, and tumorigenicity.

Original languageEnglish (US)
Pages (from-to)2162-2172
Number of pages11
JournalCancer Research
Volume66
Issue number4
DOIs
StatePublished - Feb 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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