Mutant PIK3CA promotes cell growth and invasion of human cancer cells

Yardena Samuels1, Luis A Diaz, Oleg Schmidt-Kittler

  • 1The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA.

Cancer Cell
|June 14, 2005
PubMed

Insights

Mutations in PIK3CA, common in cancers, reduce cell dependence on growth factors. This leads to less apoptosis and increased tumor invasion, offering therapeutic targets for PIK3CA-altered cancers.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The gene PIK3CA is frequently altered in various human cancers.
  • The functional consequences of PIK3CA mutations remain largely undefined.

Purpose of the Study:

  • To investigate the functional impact of the two most common PIK3CA mutations in colorectal cancer (CRC).

Main Methods:

  • Gene targeting was employed to inactivate common PIK3CA mutations in CRC cells.
  • Biochemical analyses were performed to assess signaling pathway alterations.

Main Results:

  • Mutant PIK3CA selectively regulated AKT and FKHR/FKHRL1 phosphorylation.
  • PIK3CA mutations decreased growth factor dependence and attenuated apoptosis.
  • Tumor invasion was facilitated by PIK3CA mutations.
  • The PI3K inhibitor LY294002 abrogated PIK3CA signaling and inhibited growth of mutant cells.

Conclusions:

  • PIK3CA mutations impact key cellular processes including apoptosis and invasion.
  • Targeting PI3K signaling may be a viable therapeutic strategy for cancers with PIK3CA alterations.

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