Targeting adhesion signaling in KRAS, LKB1 mutant lung adenocarcinoma.

ABSTRACT: Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre-induced Kras and Lkb1 mutant genetically engineered mouse model (KL_Lenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen. Modeling invas

SUBMITTER: Gilbert-Ross M 

PROVIDER: S-EPMC5333956 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature