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

H. Moon, C. S. Lee, K. L. Inder, S. Sharma, Eun ju Choi, D. M. Black, K. A. Lê Cao, C. Winterford, J. I. Coward, M. T. Ling, D. J. Craik, R. G. Parton, P. J. Russell, M. M. Hill

Research output: Contribution to journalArticle

37 Scopus citations

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 -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.

Original languageEnglish (US)
Pages (from-to)3561-3570
Number of pages10
JournalOncogene
Volume33
Issue number27
DOIs
StatePublished - Jul 3 2014
Externally publishedYes

Keywords

  • caveolae
  • caveolin-1
  • cavin-1
  • prostate cancer
  • PTRF

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Moon, H., Lee, C. S., Inder, K. L., Sharma, S., Choi, E. J., 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. (2014). PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer. Oncogene, 33(27), 3561-3570. https://doi.org/10.1038/onc.2013.315