Signaling networks assembled by oncogenic EGFR and c-Met

@article{citeulike:2210072, abstract = {A major question regarding the sensitivity of solid tumors to targeted kinase inhibitors is why some tumors respond and others do not. The observation that many tumors express EGF receptor (EGFR), yet only a small subset with EGFR-activating mutations respond clinically to EGFR inhibitors (EGFRIs), suggests that responsive tumors uniquely depend on EGFR signaling for their survival. The nature of this dependence is not understood. Here, we investigate dependence on EGFR signaling by comparing non-small-cell lung cancer cell lines driven by EGFR-activating mutations and genomic amplifications using a global proteomic analysis of phospho-tyrosine signaling. We identify an extensive receptor tyrosine kinase signaling network established in cells expressing mutated and activated EGFR or expressing amplified c-Met. We show that in drug sensitive cells the targeted tyrosine kinase drives other RTKs and an extensive network of downstream signaling that collapse with drug treatment. Comparison of the signaling networks in EGFR and c-Met-dependent cells identify a "core network" of {approx}50 proteins that participate in pathways mediating drug response. 10.1073/pnas.0707270105}, author = {Guo, Ailan and Villen, Judit and Kornhauser, Jon and Lee, Kimberly A. and Stokes, Matthew P. and Rikova, Klarisa and Possemato, Anthony and Nardone, Julie and Innocenti, Gregory and Wetzel, Randall and Wang, Yi and Macneill, Joan and Mitchell, Jeffrey and Gygi, Steven P. and Rush, John and Polakiewicz, Roberto D. and Comb, Michael J. }, citeulike-article-id = {2210072}, doi = {10.1073/pnas.0707270105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {experiment, sample-network}, month = {January}, pages = {0707270105+}, posted-at = {2008-01-09 07:11:00}, priority = {2}, title = {Signaling networks assembled by oncogenic EGFR and c-Met}, url = {http://dx.doi.org/10.1073/pnas.0707270105}, year = {2008} }

TY - JOUR ID - citeulike:2210072 L3 - citeulike-article-id:2210072 TI - Signaling networks assembled by oncogenic EGFR and c-Met JF - Proceedings of the National Academy of Sciences SP - 0707270105 N2 - A major question regarding the sensitivity of solid tumors to targeted kinase inhibitors is why some tumors respond and others do not. The observation that many tumors express EGF receptor (EGFR), yet only a small subset with EGFR-activating mutations respond clinically to EGFR inhibitors (EGFRIs), suggests that responsive tumors uniquely depend on EGFR signaling for their survival. The nature of this dependence is not understood. Here, we investigate dependence on EGFR signaling by comparing non-small-cell lung cancer cell lines driven by EGFR-activating mutations and genomic amplifications using a global proteomic analysis of phospho-tyrosine signaling. We identify an extensive receptor tyrosine kinase signaling network established in cells expressing mutated and activated EGFR or expressing amplified c-Met. We show that in drug sensitive cells the targeted tyrosine kinase drives other RTKs and an extensive network of downstream signaling that collapse with drug treatment. Comparison of the signaling networks in EGFR and c-Met-dependent cells identify a "core network" of {approx}50 proteins that participate in pathways mediating drug response. 10.1073/pnas.0707270105 KW - experiment KW - sample-network AU - Guo, Ailan AU - Villen, Judit AU - Kornhauser, Jon AU - Lee, Kimberly AU - Stokes, Matthew AU - Rikova, Klarisa AU - Possemato, Anthony AU - Nardone, Julie AU - Innocenti, Gregory AU - Wetzel, Randall AU - Wang, Yi AU - Macneill, Joan AU - Mitchell, Jeffrey AU - Gygi, Steven AU - Rush, John AU - Polakiewicz, Roberto AU - Comb, Michael PY - 2008/01/07/ UR - http://dx.doi.org/10.1073/pnas.0707270105 ER -