Abstract 5510: Loss of epithelial membrane protein 2 enhances Kras-driven lung tumorigenesis via FAK/AKT pathways

Abstract

Abstract Epithelial membrane protein-2 (EMP2) belongs to the growth arrest specific-3 (GAS3)/PMP22 family of tetraspan proteins. These family members are involved in the pathogenesis of human diseases, including malignancy. EMP2 is highly expressed in normal lung alveoli; however, its functional role in lung tumor is largely unknown. In this study, we focus a novel function for EMP2 in lung tumor progression. To investigate this possibility, EMP2 knock-out mice were crossed with KrasG12Dmice that carry an oncogenic mutation of the Kras gene (G12D) and develop lung adenocarcinoma. Incidence of lung tumor in KrasG12DEMP2-/- mice was higher than that in KrasG12DEMP2+/+ mice. We also found that loss of EMP2 accelerated lung tumor progression. Then, we investigated the role of EMP2 in lung cancer cell line. Expression of EMP2 was knocked out by CRISPR/Cas9 editing system in H1299 (KrasWT), H358 (KrasMut) and A549 cells (KrasMut). Loss of EMP2 induced that expression of integrin α5 is increased but expression of integrin α6 is decreased. Alteration of integrin expression activated FAK/AKT pathway. These results support the role of EMP2 loss in the control of lung cancer progression with oncogenic Kras. Taken together, these findings establish that EMP2 is a potent suppressor of Kras-driven lung tumorigenesis via FAK/AKT pathway. Citation Format: Ji Yun Jang, Mi Kyung Park, Chang Hoon Lee, Ho Lee. Loss of epithelial membrane protein 2 enhances Kras-driven lung tumorigenesis via FAK/AKT pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5510.