Enhanced MET translation and signaling sustains K-Ras driven proliferation under anchorage-independent growth conditions

摘要: Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with are resistant to chemotherapeutic drugs as well molecular targeting agents. Although numerous approaches ongoing find effective ways treat these tumors, there still no therapies for mutant cancer patients. Here we report that cancers more dependent on anchorage-independent culture conditions than monolayer conditions. In seeking determine mechanisms contribute the dependency conditions, discovered involvement Met K-Ras–dependent, cell growth. The signaling pathway is enhanced plays an indispensable role growth even cells which not amplified. Indeed, expression elevated under regulated by a MAPK/ERK kinase (MEK)-dependent manner. Remarkably, spite global downregulation mRNA translation during growth, specifically Importantly, ectopic active rescues ablation-derived suppression, indicating K-Ras–mediated drives “K-Ras addiction” Our results indicate essential suggests pharmacological inhibitors could be tumor Cancer Res; 75(14); 2851–62. ©2015 AACR .