SGK3 and INPP4B mediate PI3K signaling pathway in breast cancer


Phosphoinositide 3-kinase (PI3K) is a well-known mediator in breast cancer by increasing cell proliferation rate, survival, and metastasis level. The oncogenic mutations in the gene encoding PI3K catalytic subunit, PI3KCA, are frequently happened in breast cancers. By investigating the mechanism of PIK3CA signaling transduction, Gasser et al.  found serum/glucocorticoid-regulated kinase 3 (SGK3) and inositol polyphosphate-4-phosphatase type II (INPP4B) are two critical factors in tumors with PIK3CA mutations. Recently, the article was published online by Molecular Cell


Akt is considered to be a primary target of the PI3K signal. However, researchers found PI3K mediated PI3KCA-mutant tumorigenic signals in an Akt-independent manner. SGK3 was found to be the downstream factor of PIK3CA. The activation of SGK3 was dependent on INPP4B, which suppressed Akt phosphorylation. Further investigation showed N-Myc downstream regulated 1 (NDRG1) is a downstream signal of SGK3 in breast cancer cells. This work provides a new insight into PI3K signaling axis, with SGK3 and INPP4B as key factors and in the absence of Akt activity, for regulation of tumorigenesis, tumor cell proliferation and invasive migration.


Mol Cell. 2014 Nov 20;10.1016/j.molcel.2014.09.023

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