SGK3 Mediates INPP4B-Dependent PI3K Signaling in Breast Cancer

Jessica A. Gasser, Hiroyuki Inuzuka, Alan W. Lau, Wenyi Wei, Rameen Beroukhim, Alex Toker

研究成果: Article査読

110 被引用数 (Scopus)

抄録

Oncogenic mutations in PIK3CA, the gene encoding the catalytic subunit of phosphoinositide 3-kinase (PI3K), occur with high frequency in breast cancer. The protein kinase Akt is considered to be the primary effector of PIK3CA, although mechanisms by which PI3K mediates Akt-independent tumorigenic signals remain obscure. We show that serum and glucocorticoid-regulated kinase 3 (SGK3) is amplified in breast cancer and activated downstream of PIK3CA in a manner dependent on the phosphoinositide phosphatase INPP4B. Expression of INPP4B leads to enhanced SGK3 activation and suppression of Akt phosphorylation. Activation of SGK3 downstream of PIK3CA and INPP4B is required for 3D proliferation, invasive migration, and tumorigenesis invivo. We further show that SGK3 targets the metastasis suppressor NDRG1 for degradation by Fbw7. We propose a model in which breast cancersharboring oncogenic PIK3CA activate SGK3 signaling while suppressing Akt, indicative of oncogenic functions for both INPP4B and SGK3 in these tumors.

本文言語English
ページ(範囲)595-607
ページ数13
ジャーナルMolecular Cell
56
4
DOI
出版ステータスPublished - 2014 11月 20
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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