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

doi:10.1016/j.ccr.2005.05.014

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 journal › Article › peer-review

693 Scopus citations

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 language	English (US)
Pages (from-to)	561-573
Number of pages	13
Journal	Cancer cell
Volume	7
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2005.05.014
State	Published - Jun 2005

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2005.05.014

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@article{814053b5c7d44da7bf304cb7f944ca2e,

title = "Mutant PIK3CA promotes cell growth and invasion of human cancer cells",

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.",

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

note = "Funding Information: The authors thank Zhenghe Wang, Marcelo Reis, and Mark Behlke for advice, and Natalie Silliman, Janine Ptak, Steve Szabo, and Latice Watson for technical assistance. This work was supported by the Ludwig Trust, The Pew Charitable Trusts, and NIH grants CA43460, CA62924, and CA057345. Y.S. is an EMBO fellow. ",

year = "2005",

month = jun,

doi = "10.1016/j.ccr.2005.05.014",

language = "English (US)",

volume = "7",

pages = "561--573",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Mutant PIK3CA promotes cell growth and invasion of human cancer cells

AU - Samuels, Yardena

AU - Diaz, Luis A.

AU - Schmidt-Kittler, Oleg

AU - Cummins, Jordan M.

AU - DeLong, Laura

AU - Cheong, Ian

AU - Rago, Carlo

AU - Huso, David L.

AU - Lengauer, Christoph

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Velculescu, Victor E.

N1 - Funding Information: The authors thank Zhenghe Wang, Marcelo Reis, and Mark Behlke for advice, and Natalie Silliman, Janine Ptak, Steve Szabo, and Latice Watson for technical assistance. This work was supported by the Ludwig Trust, The Pew Charitable Trusts, and NIH grants CA43460, CA62924, and CA057345. Y.S. is an EMBO fellow.

PY - 2005/6

Y1 - 2005/6

N2 - 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.

AB - 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.

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DO - 10.1016/j.ccr.2005.05.014

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AN - SCOPUS:20444374445

SN - 1535-6108

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SP - 561

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JO - Cancer cell

JF - Cancer cell

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ER -

Mutant PIK3CA promotes cell growth and invasion of human cancer cells

Abstract

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