Abstract 5882: FAK is required for the survival of tumor cells in MMTV-Wnt1 driven basal-like mammary tumors

Abstract

Abstract Breast cancer is a heterogeneous disease. Stratification of patients based on the subtype of breast cancer is a key to successful treatment of breast cancer. Focal Adhesion Kinase (FAK), a cytoplasmic tyrosine kinase is over expressed and activated in several cancers including breast cancer. Our earlier studies have shown inhibition of FAK in MMTV-PyMT mouse mammary tumors that are classified as Luminal B subtype, delays tumor onset and reduces tumor growth. To address whether inhibition of FAK would be beneficial in basal-like mammary tumors, we generated a conditional deletion of FAK and a knock in mutation of FAK lacking its kinase activity, in MMTV-WNT1 mouse model, which classifies as basal-like. Similar to PyMT mammary tumors we found that loss of FAK or its kinase function delays tumor onset and tumor growth of basal like WNT1 mammary tumors. However unlike the PyMT tumors, the reduced tumor growth in WNT1 model is not due to decreased proliferation. Interestingly loss of FAK activity in WNT1 tumors results in accumulation of cleaved caspase 3, suggesting that loss of FAK activity results in compromised tumor cell survival. When we investigated the pathways through which FAK could affect survival, we found that loss of FAK activity reduces activation of AKT. Reduced AKT activation induces the expression of pro-apoptotic genes. In summary our studies show that in a basal-like tumor model, FAK is required for survival of the tumor cells. Hence inhibition of FAK could be beneficial for elimination of basal-like tumor cells. Citation Format: Ritama Paul, Syn K. Yeo, Ming Luo, Susan Waltz, Jun-Lin Guan. FAK is required for the survival of tumor cells in MMTV-Wnt1 driven basal-like mammary tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5882. doi:10.1158/1538-7445.AM2017-5882