Expression of PTRF in PC3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways

Inder, Kerry L, Zheng, Yu Zi, Davis, Melissa J, Moon, Hyeongsun, Loo, Dorothy, Nguyen, Hien, Clements, Judith A., Parton, Robert G, Foster, Leonard J, & Hill, Michelle M (2012) Expression of PTRF in PC3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Molecular and Cellular Proteomics, 11(2).

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Expression of caveolin-1 is up-regulated in prostate cancer metastasis and is associated with aggressive recurrence of the disease. Intriguingly, caveolin-1 is also secreted from prostate cancer cell lines and has been identified in secreted prostasomes. Caveolin-1 is the major structural component of the plasma membrane invaginations called caveolae. Co-expression of the coat protein Polymerase I and transcript release factor (PTRF) is required for caveolae formation. We recently found that expression of caveolin-1 in the aggressive prostate cancer cell line PC-3 is not accompanied by PTRF, leading to noncaveolar caveolin-1 lipid rafts. Moreover, ectopic expression of PTRF in PC-3 cells sequesters caveolin-1 into caveolae. Here we quantitatively analyzed the effect of PTRF expression on the PC-3 proteome using stable isotope labeling by amino acids in culture and subcellular proteomics. We show that PTRF reduced the secretion of a subset of proteins including secreted proteases, cytokines, and growth regulatory proteins, partly via a reduction in prostasome secretion. To determine the cellular mechanism accounting for the observed reduction in secreted proteins we analyzed total membrane and the detergent-resistant membrane fractions. Our data show that PTRF expression selectively impaired the recruitment of actin cytoskeletal proteins to the detergent-resistant membrane, which correlated with altered cholesterol distribution in PC-3 cells expressing PTRF. Consistent with this, modulating cellular cholesterol altered the actin cytoskeleton and protein secretion in PC-3 cells. Intriguingly, several proteins that function in ER to Golgi trafficking were reduced by PTRF expression. Taken together, these results suggest that the noncaveolar caveolin-1 found in prostate cancer cells generates a lipid raft microenvironment that accentuates secretion pathways, possibly at the step of ER sorting/exit. Importantly, these effects could be modulated by PTRF expression.

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30 citations in Scopus
5 citations in Web of Science®
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ID Code: 54792
Item Type: Journal Article
Refereed: Yes
Keywords: PTRF, PC3 Cells, cholesterol, actin cytoskeleton, secretion pathways
DOI: 10.1074/mcp.M111.012245
ISSN: 1535-9476
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 American Society for Biochemistry and Molecular Biology, Inc.
Copyright Statement: This research was originally published in Molecular and Cellular Proteomics. Kerry L. Inder, Yu Zi Zheng, Melissa J. Davis, Hyeongsun Moon, Dorothy Loo, Hien Nguyen, Judith A. Clements, Robert G. Parton, Leonard J. Foster, Michelle M. Hill1. Expression of PTRF in PC3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Molecular and Cellular Proteomics. 2012. Vol: 11. © the American Society for Biochemistry and Molecular Biology
Deposited On: 20 Nov 2012 23:48
Last Modified: 05 Feb 2013 05:23

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