Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response.

ABSTRACT: EGFR activation is both a key molecular driver of disease progression and the target of a broad class of molecular agents designed to treat advanced cancer. Nevertheless, resistance develops through several mechanisms, including activation of AKT signaling. Though much is known about the specific molecular lesions conferring resistance to anti-EGFR-based therapies, additional molecular characterization of the downstream mediators of EGFR signaling may lead to the development of new classes of targeted molecular therapies to treat resistant disease. We identified a transcriptional network involving the tumor suppressors Krüppel-like factor 6 (KLF6) and forkhead box O1 (FOXO1) that negatively regulates activated EGFR signaling in both cell culture and in vivo models. Furthermore, the use of

SUBMITTER: Sangodkar J 

PROVIDER: S-EPMC3386822 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature