Abstract 3040: Cavin-1 alters oncogenic effects of caveolin-1 microdomains in prostate cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Caveolin-1 is associated with prostate cancer progression and has been suggested to be a biomarker and therapeutic target. Mature caveolin-1 resides in lipid raft domains at the plasma membrane, where it forms caveolae upon co-expression of cavin-1 (also known as PTRF; polymerase I and transcript release factor). In the absence of cavin-1, caveolin-1 does not form caveolae but are found on flat membrane. To determine if oncogenic caveolin-1 in prostate cancer is present in caveolae, we examined the relative expression of caveolin-1 and cavin-1 in normal, non-malignant and malignant prostate tissues. We found that caveolin-1 is induced in prostate cancer without cavin-1, an expression pattern mirror in the PC3 cell line. Previously we showed that expression of cavin-1 in PC3 cells recruits flat membrane caveolin-1 to caveolae and reduced transmigration. Here we report that cavin-1 expression reduces tumour size and metastasis of PC3 cells in vivo, using an orthotopic prostate cancer xenograft mouse model. To determine if cavin-1 acts by neutralizing oncogenic caveolin-1, we expressed cavin-1 in caveolin-1 negative LNCaP and 22Rv1 cells. While caveolin-1 over-expression increased anchorage-independent growth of LNCaP and 22Rv1 cells, cavin-1 over-expression had no effect. Furthermore, co-expression of cavin-1 in LNCaP+caveolin-1 cells reversed caveolin-1 effect. Taken together, these results suggest that caveolin-1 in prostate cancer is present outside of caveolae, and caveola formation by cavin-1 co-expression alters the oncogenic effect of non-caveolar caveolin-1 microdomains. Citation Format: Hyeongsun Moon, C Soon Lee, Sowmya Sharma, Kerry Inder, Debra Black, Kim-Anh Le Cao, Clay Winterford, Patrick Ling, the Australian Prostate Cancer BioResource, David Craik, Robert Parton, Pamela Russell, Michelle Hill. Cavin-1 alters oncogenic effects of caveolin-1 microdomains in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3040. doi:10.1158/1538-7445.AM2013-3040