LAUSR

Preventing progression from non-muscle invasive to muscle invasive bladder cancer (BC) is a major clinical priority. This transition is defined by tumor invasion through the bladder epithelium basement membrane into the lamina propria and muscle wall. Inhibition of SRC, a pro-invasion, non-receptor tyrosine kinase that signals as part of a complex with Focal Adhesion Kinase (FAK), may prevent BC progression. We hypothesize that SRC inhibition will disrupt migration and invasion of BC cells. Using The Cancer Genome Atlas (TCGA) mRNA expression data of human bladder tumors, we generated a classifier to subtype tumors as either “luminal” or “basal” and compared SRC expression between the groups. We then sequenced a panel of 30 bladder cancer cell lines. Each cell line was given a subtype call based on our luminal- basal classifier, and levels of SRC mRNA expression were examined. To determine the impact of SRC inhibition on luminal and basal subtypes, we exposed BC cell lines to the SRC-Family Kinase inhibitor, AZD0530. The impact of SRC inhibition on proliferation was measured by MTT assay. Transwell assays were used to examine the effect of SRC inhibition on migration, collagen invasion, and Matrigel invasion. Phosphorylation of SRC downstream targets after AZD0530 treatment was assessed by western blot. The role of SRC target and signaling partner FAK in migration was determined by siRNA knockdown and transwell assay. Luminal human bladder tumors had significantly greater SRC mRNA expression than basal tumors (p Citation Format: Bryan Wehrenberg, Andrea Ochoa, Woonyoung Choi, David McConkey. SRC drives invasion of luminal, but not basal, bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4589.