Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 17, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/ijms17071061
Keywords
prostate cancer; lipogenesis; fatty acid oxidation; carnitine palmitoyltransferase (CPT1); hypoxia; re-oxygenation; extracellular vesicles
Funding
- K01 grant [CA168934]
- R21 grant [CA199628]
- DOD [W81XWH-15-1-0188]
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Prostate cancer (PCa) is the leading malignancy among men in United States. Recent studies have focused on the identification of novel metabolic characteristics of PCa, aimed at devising better preventive and therapeutic approaches. PCa cells have revealed unique metabolic features such as higher expression of several enzymes associated with de novo lipogenesis, fatty acid up-take and -oxidation. This aberrant lipid metabolism has been reported to be important for PCa growth, hormone-refractory progression and treatment resistance. Furthermore, PCa cells effectively use lipid metabolism under adverse environmental conditions for their survival advantage. Specifically, hypoxic cancer cells accumulate higher amount of lipids through a combination of metabolic alterations including high glutamine and fatty acid uptake, as well as decreased fatty acid oxidation. These stored lipids serve to protect cancer cells from oxidative and endoplasmic reticulum stress, and play important roles in fueling cancer cell proliferation following re-oxygenation. Lastly, cellular lipids have also been implicated in extracellular vesicle biogenesis, which play a vital role in intercellular communication. Overall, the new understanding of lipid metabolism in recent years has offered several novel targets to better target and manage clinical PCa.
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