| Literature DB >> 20541700 |
Julian Carretero1, Takeshi Shimamura, Klarisa Rikova, Autumn L Jackson, Matthew D Wilkerson, Christa L Borgman, Matthew S Buttarazzi, Benjamin A Sanofsky, Kate L McNamara, Kathleyn A Brandstetter, Zandra E Walton, Ting-Lei Gu, Jeffrey C Silva, Katherine Crosby, Geoffrey I Shapiro, Sauveur-Michel Maira, Hongbin Ji, Diego H Castrillon, Carla F Kim, Carlos García-Echeverría, Nabeel Bardeesy, Norman E Sharpless, Neil D Hayes, William Y Kim, Jeffrey A Engelman, Kwok-Kin Wong.
Abstract
In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment. Copyright 2010 Elsevier Inc. All rights reserved.Entities:
Mesh：
Substances：
Year: 2010 PMID： 20541700 PMCID： PMC2901842 DOI： 10.1016/j.ccr.2010.04.026
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743