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

Moon, H., Lee, C. S., Inder, K. L., Sharma, S., Choi, E., Black, D. M., Lê Cao, K.-A., Winterford, C., Coward, J. I., Ling, M. T., Craik, D. J., Parton, R. G., Russell, P.J., Hill, M. M. and The Australian Prostate Cancer BioResource (2014) PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer. Oncogene, 33 27: 3561-3570. doi:10.1038/onc.2013.315

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Author Moon, H.
Lee, C. S.
Inder, K. L.
Sharma, S.
Choi, E.
Black, D. M.
Lê Cao, K.-A.
Winterford, C.
Coward, J. I.
Ling, M. T.
Craik, D. J.
Parton, R. G.
Russell, P.J.
Hill, M. M.
The Australian Prostate Cancer BioResource
Title PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1038/onc.2013.315
Volume 33
Issue 27
Start page 3561
End page 3570
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Keyword PTRF
Prostate cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication 12 August 2013

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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 22 Nov 2013, 21:59:50 EST by Susan Allen on behalf of UQ Diamantina Institute