| Literature DB >> 19573809 |
Krishna M Vasudevan1, David A Barbie, Michael A Davies, Rosalia Rabinovsky, Chontelle J McNear, Jessica J Kim, Bryan T Hennessy, Hsiuyi Tseng, Panisa Pochanard, So Young Kim, Ian F Dunn, Anna C Schinzel, Peter Sandy, Sebastian Hoersch, Qing Sheng, Piyush B Gupta, Jesse S Boehm, Jan H Reiling, Serena Silver, Yiling Lu, Katherine Stemke-Hale, Bhaskar Dutta, Corwin Joy, Aysegul A Sahin, Ana Maria Gonzalez-Angulo, Ana Lluch, Lucia E Rameh, Tyler Jacks, David E Root, Eric S Lander, Gordon B Mills, William C Hahn, William R Sellers, Levi A Garraway.
Abstract
Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth. Instead, these cells retain robust PDK1 activation and membrane localization and exhibit dependency on the PDK1 substrate SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PIK3CA mutant cancer cells. Thus, PI3K may promote cancer through both AKT-dependent and AKT-independent mechanisms. Knowledge of differential PI3K/PDK1 signaling could inform rational therapeutics in cancers harboring PIK3CA mutations.Entities:
Mesh：
Substances：
Year: 2009 PMID： 19573809 PMCID： PMC2752826 DOI： 10.1016/j.ccr.2009.04.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743