Caveola-forming proteins and prostate cancer
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Caveola-forming proteins and prostate cancer Zeyad D. Nassar 1,2
&
Marie-Odile Parat 3
# Springer Science+Business Media, LLC, part of Springer Nature 2020
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 caveolaforming 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. Keywords Caveolae . Caveolin-1 . Cavin-1 . Prostate cancer
1 Introduction Prostate cancer (PCa) is the most diagnosed cancer and the second leading cause of cancer-related death in men in Western countries [1]. Introducing the PSA test in the early 1990s has facilitated the disease diagnosis at very early stages, giving patients the opportunity to opt for active surveillance and to avoid the side effects of treatment. However, a subset of those patients have a high risk to develop aggressive tumours and would have benefited from a prompt treatment at the time of diagnosis. Since the 1940s, androgen deprivation therapy has been established as a main strategy to manage PCa, yet it
* Zeyad D. Nassar [email protected] 1
Adelaide Medical School and Freemasons Foundation Centre for Men’s Health, University of Adelaide, Adelaide 5000, Australia
2
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
3
School of Pharmacy, University of Queensland , 20 Cornwall Street, Woolloongabba, QLD 4102, Australia
impacts patient quality of life and inevitably all patients develop resistance against therapy and progress to the deadly incurable castrate-resistant prostate cancer (CRPC) stage. Discovering biomarkers that can identify patients with a high risk of developing aggressive disease and new therapeutic targets that can delay and treat CRPC is necessary to improv
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