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Caveola-forming proteins and prostate cancer

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Abstract

Caveolae are specialised and dynamic plasma membrane subdomains, involved in many cellular functions including endocytosis, signal transduction, mechanosensing and lipid storage, trafficking, and metabolism. Two protein families are indispensable for caveola formation and function, namely caveolins and cavins. Mutations of genes encoding these caveolar proteins cause serious pathological conditions such as cardiomyopathies, skeletal muscle diseases, and lipodystrophies. Deregulation of caveola-forming protein expression is associated with many types of cancers including prostate cancer. The distinct function of secretion of the prostatic fluid, and the unique metabolic phenotype of prostate cells relying on lipid metabolism as a main bioenergetic pathway further suggest a significant role of caveolae and caveolar proteins in prostate malignancy. Accumulating in vitro, in vivo, and clinical evidence showed the association of caveolin-1 with prostate cancer grade, stage, metastasis, and drug resistance. In contrast, cavin-1 was found to exhibit tumour suppressive roles. Studies on prostate cancer were the first to show the distinct function of the caveolar proteins depending on their localisation within the caveolar compartment or as cytoplasmic or secreted proteins. In this review, we summarise the roles of caveola-forming proteins in prostate cancer and the potential of exploiting them as therapeutic targets or biological markers.

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Acknowledgments

The results shown here are in whole or part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

Funding

ZDN is supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia (1138648), a John Mills Young Investigator Award from the Prostate Cancer Foundation of Australia (YI 1417), and the Cure Cancer Australia Priority-driven Collaborative Cancer Research Scheme (1164798).

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  1. Adelaide Medical School and Freemasons Foundation Centre for Men’s Health, University of Adelaide, Adelaide, 5000, Australia

    Zeyad D. Nassar

  2. Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia

    Zeyad D. Nassar

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

    Marie-Odile Parat

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Nassar, Z.D., Parat, MO. Caveola-forming proteins and prostate cancer. Cancer Metastasis Rev 39, 415–433 (2020). https://doi.org/10.1007/s10555-020-09874-x

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