Poster Presentation 25th Lorne Cancer Conference 2013

Cavin-1 alters oncogenic effects of caveolin-1 microdomains in prostate cancer (#284)

Hyeongsun Moon 1 , C Soon Lee 2 , Sowmya Sharma 2 , Kerry L Inder 1 , Debra M Black 1 , Kim-Anh Lê Cao 3 , Clay Winterford 4 , Patrick Ling 5 , the Australian Prostate Cancer BioResource , David J Craik 6 , Robert G Parton 6 , Pamela J Russell 5 , Michelle M Hill 1
  1. Diamantina Institute, Woolloongabba , QLD, Australia
  2. Discipline of Pathology, School of Medicine and Molecular Medicine Research Group, University of Western Sydney, Sydney, New South Wales, Australia
  3. Queensland Facility for Advanced Bioinformatics, The University of Queensland, Brisbane, Australia
  4. School of Medicine , The University of Queensland, Brisbane, Australia
  5. Australian Prostate Cancer Research Centre–Queensland and Institute for Biomedical Health & Innovation, Queensland University of Technology, Woolloongabba, Australia
  6. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

Caveolin-1 is associated with prostate cancer progression and has been suggested to be a biomarker and therapeutic target1. 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 membrane2. 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 caveolae2  and reduced transmigration3. 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.

  1. Yang et al. Mol Cancer Res. 2012. Caveolin-1 upregulation contributes to c-Myc-induced high-grade prostatic intraepithelial neoplasia and prostate cancer.
  2. Hill et al. Cell. 2008. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function
  3. Aung et al. Eur J Cell Biol. 2011. PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9.