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Caveola-forming proteins caveolin-1 and PTRF in prostate cancer

Nature Reviews Urology volume 10, pages 529–536 (2013)Cite this article

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Abstract

The expression of caveola-forming proteins is dysregulated in prostate cancer. Caveolae are flask-shaped invaginations of the plasma membrane that have roles in membrane trafficking and cell signalling. Members of two families of proteins—caveolins and cavins—are known to be required for the formation and functions of caveolae. Caveolin-1, the major structural protein of caveolae, is overexpresssed in prostate cancer and has been demonstrated to be involved in prostate cancer angiogenesis, growth and metastasis. Polymerase I and transcript release factor (PTRF) is the only cavin family member necessary for caveola formation. When exogenously expressed in prostate cancer cells, PTRF reduces aggressive potential, probably via both caveola-mediated and caveola-independent mechanisms. In addition, stromal PTRF expression decreases with progression of the disease. Evaluation of caveolin-1 antibodies in the clinical setting is underway and it is hoped that future studies will reveal the mechanisms of PTRF action, allowing its targeting for therapeutic purposes.

Key Points

  • Caveolae are flask-shaped plasma membrane invaginations, the formation of which requires two families of proteins, the membrane-inserted caveolins and cytoplasmic cavins

  • Caveolin-1, the major caveolin family member, is overexpressed in prostate cancer and promotes tumour growth, angiogenesis and insensitivity to androgen deprivation

  • Caveolin-1 can be secreted and exert paracrine and endocrine effects that contribute to prostate tumour growth and metastasis

  • Expression of polymerase I and transcript release factor (PTRF) is reported to be absent in prostate cancer

  • Exogenous expression of PTRF reduces prostate cancer aggressiveness probably via both caveola-mediated and caveola-independent mechanisms

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Figure 1: Caveola formation requires membrane-inserted caveolin-1 and cytoplasmic PTRF.

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Authors and Affiliations

  1. School of Pharmacy, The University of Queensland, 20 Cornwall Street, Woolloongabba, 4102, QLD, Australia

    Zeyad D. Nassar & Marie-Odile Parat

  2. The University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Woolloongabba, 4102, QLD, Australia

    Michelle M. Hill

  3. Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, The University of Queensland, 4072, QLD, Australia

    Robert G. Parton

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  1. Zeyad D. Nassar
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  2. Michelle M. Hill
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  4. Marie-Odile Parat
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Z. D. Nessar and M.-O. Parat researched data for the article and wrote the article. All authors contributed to discussion of content. M.-O. Parat, M. M. Hill and R. G. Parton reviewed the manuscript before submission.

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Correspondence to Marie-Odile Parat.

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Nassar, Z., Hill, M., Parton, R. et al. Caveola-forming proteins caveolin-1 and PTRF in prostate cancer. Nat Rev Urol 10, 529–536 (2013). https://doi.org/10.1038/nrurol.2013.168

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