Mutant PIK3CA promotes cell growth and invasion of human cancer cells

Yardena Samuels, Luis A. Diaz, Oleg Schmidt-Kittler, Jordan M. Cummins, Laura DeLong, Ian Cheong, Carlo Rago, David L. Huso, Christoph Lengauer, Kenneth W. Kinzler, Bert Vogelstein, Victor E. Velculescu

Research output: Contribution to journalArticle

Abstract

PIK3CA is mutated in diverse human cancers, but the functional effects of these mutations have not been defined. To evaluate the consequences of PIK3CA alterations, the two most common mutations were inactivated by gene targeting in colorectal cancer (CRC) cells. Biochemical analyses of these cells showed that mutant PIK3CA selectively regulated the phosphorylation of AKT and the forkhead transcription factors FKHR and FKHRL1. PIK3CA mutations had little effect on growth under standard conditions, but reduced cellular dependence on growth factors. PIK3CA mutations resulted in attenuation of apoptosis and facilitated tumor invasion. Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells. These data have important implications for therapy of cancers harboring PIK3CA alterations.

Original languageEnglish (US)
Pages (from-to)561-573
Number of pages13
JournalCancer cell
Volume7
Issue number6
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., Vogelstein, B., & Velculescu, V. E. (2005). Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer cell, 7(6), 561-573. https://doi.org/10.1016/j.ccr.2005.05.014