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

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.

• Authors: H Moon, C S Lee, K L Inder, S Sharma, E Choi, D M Black, K-A Lê Cao, C Winterford, J I Coward, M T Ling, Australian Prostate Cancer BioResource, D J Craik, R G Parton, P J Russell, M M Hill
• Journal: Oncogene (Oncogene) Vol. 33 Issue 27 Pg. 3561-70 (Jul 03 2014) ISSN: 1476-5594 [Electronic] England
• PMID: 23934189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ACTA2 protein, human
• Actins
• CAVIN1 protein, human
• Caveolin 1
• Interleukin-6
• RNA-Binding Proteins
• Receptors, Androgen
• Proto-Oncogene Proteins c-akt

Topics

• Actins (metabolism)
• Aged
• Animals
• Caveolin 1 (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Cell Transformation, Neoplastic
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-6 (metabolism)
• Male
• Membrane Microdomains (metabolism)
• Mice
• Middle Aged
• Neoplasm Metastasis
• Phosphorylation
• Prostatic Neoplasms (metabolism, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA-Binding Proteins (metabolism)
• Receptors, Androgen (metabolism)