Krishna M Vasudevan, 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
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...
July 7, 2009: Cancer Cell