Activation of the PI3K Pathway in Cancer Through Inhibition of PTEN by Exchange Factor P-REX2a

被引：176

作者：

Fine, Barry ^{[1
,2
]}

Hodakoski, Cindy ^{[1
,2
]}

Koujak, Susan ^{[1
,2
]}

Su, Tao ^{[1
,2
,3
]}

Saal, Lao H. ^{[1
,2
]}

Maurer, Matthew ^{[1
,2
,5
]}

Hopkins, Benjamin ^{[1
,2
]}

Keniry, Megan ^{[1
,2
]}

Sulis, Maria Luisa ^{[1
,2
,4
]}

Mense, Sarah ^{[1
,2
]}

Hibshoosh, Hanina ^{[1
,2
,3
]}

Parsons, Ramon ^{[1
,2
,3
,5
]}

机构：

[1] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA

[2] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[3] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA

[4] Columbia Univ, Med Ctr, Div Pediat Oncol, New York, NY 10032 USA

[5] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA

来源：

SCIENCE | 2009年 / 325卷 / 5945期

关键词：

BREAST-CANCER; GENETIC ALTERATIONS; TUMOR-SUPPRESSOR; PROSTATE-CANCER; RAC; CELLS; PHOSPHATASE; MUTATIONS;

D O I：

10.1126/science.1173569

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

PTEN (phosphatase and tensin homolog on chromosome 10) is a tumor suppressor whose cellular regulation remains incompletely understood. We identified phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) as a PTEN-interacting protein. P-REX2a mRNA was more abundant in human cancer cells and significantly increased in tumors with wild-type PTEN that expressed an activated mutant of PIK3CA encoding the p110 subunit of phosphoinositide 3-kinase subunit alpha (PI3K alpha). P-REX2a inhibited PTEN lipid phosphatase activity and stimulated the PI3K pathway only in the presence of PTEN. P-REX2a stimulated cell growth and cooperated with a PIK3CA mutant to promote growth factor-independent proliferation and transformation. Depletion of P-REX2a reduced amounts of phosphorylated AKT and growth in human cell lines with intact PTEN. Thus, P-REX2a is a component of the PI3K pathway that can antagonize PTEN in cancer cells.

引用

页码：1261 / 1265

页数：5

共 23 条

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