Abstract 1160: FRY Inhibits progression and metastasis of breast cancer through activating Hippo signaling pathway

Background: Recently, we reported that using quantitative trait locus (QTL) mapping in differentially susceptible rat strains, we identified Fry, the mammalian ortholog of the furry gene in Drosophila melanoganster, as a candidate mammary carcinoma susceptibility gene (Mcs30). Preliminary studies of rat Fry gene suggest that Fry may play a key role in epithelial-mesenchymal transition (EMT), tumor progression and metastasis. Methods: In the present study, we modified and established multiple breast cancer cell lines with enhanced expression of either wildtype or mutated human FRY gene. We examined the anti-tumorigenic and anti-metastatic effects of enhanced FRY expression on these cell lines in vitro and in vivo. We also utilized RNA-seq and proteomic approach to dissect FRY-regulated signaling molecules and pathways. Results: Ectopic expression of wild-type FRY significantly diminished tumorigenicity and metastasis of breast cancer cells both in vitro and in animal studies, particularly in the triple negative breast cancer cell line, MDA-MB-231 cells. Relative to the rapidly tumors growth of MDA-MB-231 cells in vitro and in nude mice assay, the growth of MDA-MB-231 cells ectopically expressing the FRY significantly reduced. In comparison, the anti-tumorigenic effects of mutated FRY were compromised but remained significant. Further, we showed that FRY9s effects in suppressing proliferation, invasion, and metastasis of breast cancer cells were partially through the activation of Hippo signaling pathway. Conclusions: These results provide direct evidence in supporting the important role of FRY in breast cancer progression and metastasis, and first time reveal a connection between FRY and the Hippo signaling pathway. Citation Format: Hao Zhang, Fan Fei, Xushen Chen, Zi Ceng, Xiaojiang Tang, Helmut Zarbl, Xuefeng Ren. FRY Inhibits progression and metastasis of breast cancer through activating Hippo signaling pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1160.