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PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer

Oncogene volume 33, pages 3561–3570 (2014)Cite this article

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Abstract

Caveolin-1 has a complex role in prostate cancer and has been suggested to be a potential biomarker and therapeutic target. As mature caveolin-1 resides in caveolae, invaginated lipid raft domains at the plasma membrane, caveolae have been suggested as a tumor-promoting signaling platform in prostate cancer. However, caveola formation requires both caveolin-1 and cavin-1 (also known as PTRF; polymerase I and transcript release factor). Here, we examined the expression of cavin-1 in prostate epithelia and stroma using tissue microarray including normal, non-malignant and malignant prostate tissues. We found that caveolin-1 was induced without the presence of cavin-1 in advanced prostate carcinoma, an expression pattern mirrored in the PC-3 cell line. In contrast, normal prostate epithelia expressed neither caveolin-1 nor cavin-1, while prostate stroma highly expressed both caveolin-1 and cavin-1. Utilizing PC-3 cells as a suitable model for caveolin-1-positive advanced prostate cancer, we found that cavin-1 expression in PC-3 cells inhibits anchorage-independent growth, and reduces in vivo tumor growth and metastasis in an orthotopic prostate cancer xenograft mouse model. The expression of α-smooth muscle actin in stroma along with interleukin-6 (IL-6) in cancer cells was also decreased in tumors of mice bearing PC-3-cavin-1 tumor cells. To determine whether cavin-1 acts by neutralizing caveolin-1, we expressed cavin-1 in caveolin-1-negative prostate cancer LNCaP and 22Rv1 cells. Caveolin-1 but not cavin-1 expression increased anchorage-independent growth in LNCaP and 22Rv1 cells. Cavin-1 co-expression reversed caveolin-1 effects in caveolin-1-positive LNCaP cells. Taken together, these results suggest that caveolin-1 in advanced prostate cancer is present outside of caveolae, because of the lack of cavin-1 expression. Cavin-1 expression attenuates the effects of non-caveolar caveolin-1 microdomains partly via reduced IL-6 microenvironmental function. With circulating caveolin-1 as a potential biomarker for advanced prostate cancer, identification of the molecular pathways affected by cavin-1 could provide novel therapeutic targets.

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Acknowledgements

We thank Duka Skalamera and Mareike Dahmer of the UQDI ARVEC facility for producing lentivirus, and the participants who kindly donated tissues to the Australian Prostate Cancer BioResource. This work was supported by project grants from the Association for International Cancer Research and Prostate Cancer Foundation Australia. MMH received a Career Development Award from the National Health and Medical Research Council of Australia (no. 569512). RGP was supported by NHMRC Project Grant 631371 and an NHMRC Australia Fellowship (569452). HM is supported by University of Queensland International Postgraduate Research Scholarship. The Australian Prostate Cancer BioResource is supported by an NHMRC Enabling Grant (no. 614296) and by an infrastructure grant from the Prostate Cancer Foundation of Australia. The ARVEC facility received support from the Australian Cancer Research Foundation.

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Authors and Affiliations

  1. The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia

    H Moon, K L Inder, E Choi, D M Black & M M Hill

  2. Discipline of Pathology, School of Medicine and Molecular Medicine Research Group, University of Western Sydney, Sydney, New South Wales, Australia

    C S Lee & S Sharma

  3. Department of Anatomical Pathology, Liverpool Hospital, Sydney, New South Wales, Australia

    C S Lee & S Sharma

  4. School of Veterinary Science, The University of Queensland, Brisbane, Queensland, Australia

    E Choi

  5. Queensland Facility for Advanced Bioinformatics, The University of Queensland, Brisbane, Queensland, Australia

    K-A Lê Cao

  6. School of Medicine, The University of Queensland, Brisbane, Queensland, Australia

    C Winterford

  7. Mater Research, Translational Research Institute, Brisbane, Queensland, Australia

    J I Coward

  8. Australian Prostate Cancer Research Centre–Queensland and Institute for Biomedical Health & Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, Queensland, Australia

    M T Ling & P J Russell

  9. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia

    D J Craik & R G Parton

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Moon, H., Lee, C., Inder, K. et al. PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer. Oncogene 33, 3561–3570 (2014). https://doi.org/10.1038/onc.2013.315

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