Extracellular Fatty Acids Are the Major Contributor to Lipid Synthesis in Prostate Cancer
| Autor: | Zeyad D. Nassar, Meghna S. Kakani, Andrew J. Hoy, Hui-Ming Lin, Jeff Holst, Lisa S. Lee, Robert F. Shearer, Lisa G. Horvath, Darren N. Saunders, Elham Hosseini-Beheshti, Margaret M. Centenera, Lisa M. Butler, Seher Balaban, Shilpa R. Nagarajan, Mark Schreuder, Nikki L. Raftopulos, Frank Liu-Fu, Atqiya Aishah, Bianca Varney, Alison Yan Zhang, Rae-Anne Hardie |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research Palmitates 03 medical and health sciences Prostate cancer 0302 clinical medicine Prostate Cell Line Tumor LNCaP medicine Extracellular Humans Molecular Biology Triglycerides Chemistry Fatty Acids Prostatic Neoplasms Extracellular Fluid Lipid metabolism Metabolism Lipid Metabolism medicine.disease Lipids 3. Good health 030104 developmental biology medicine.anatomical_structure Oncology Apoptosis Cell culture 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Molecular Cancer Research. 17:949-962 |
| ISSN: | 1557-3125 1541-7786 |
| DOI: | 10.1158/1541-7786.mcr-18-0347 |
| Popis: | Prostate cancer cells exhibit altered cellular metabolism but, notably, not the hallmarks of Warburg metabolism. Prostate cancer cells exhibit increased de novo synthesis of fatty acids (FA); however, little is known about how extracellular FAs, such as those in the circulation, may support prostate cancer progression. Here, we show that increasing FA availability increased intracellular triacylglycerol content in cultured patient-derived tumor explants, LNCaP and C4-2B spheroids, a range of prostate cancer cells (LNCaP, C4-2B, 22Rv1, PC-3), and prostate epithelial cells (PNT1). Extracellular FAs are the major source (∼83%) of carbons to the total lipid pool in all cell lines, compared with glucose (∼13%) and glutamine (∼4%), and FA oxidation rates are greater in prostate cancer cells compared with PNT1 cells, which preferentially partitioned extracellular FAs into triacylglycerols. Because of the higher rates of FA oxidation in C4-2B cells, cells remained viable when challenged by the addition of palmitate to culture media and inhibition of mitochondrial FA oxidation sensitized C4-2B cells to palmitate-induced apoptosis. Whereas in PC-3 cells, palmitate induced apoptosis, which was prevented by pretreatment of PC-3 cells with FAs, and this protective effect required DGAT-1–mediated triacylglycerol synthesis. These outcomes highlight for the first-time heterogeneity of lipid metabolism in prostate cancer cells and the potential influence that obesity-associated dyslipidemia or host circulating has on prostate cancer progression. Implications: Extracellular-derived FAs are primary building blocks for complex lipids and heterogeneity in FA metabolism exists in prostate cancer that can influence tumor cell behavior. |
| Databáze: | OpenAIRE |
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