Dietary palmitate cooperates with Src kinase to promote prostate tumor progression |
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Authors: | Sungjin Kim Xiangkun Yang Amelia Yin Junyi Zha Zanna Beharry Aiping Bai Alicja Bielawska Michael G Bartlett Hang Yin Houjian Cai |
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Institution: | 1. Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia;2. Department of Biochemistry and Molecular Biology, Center for Molecular Medicine, University of Georgia, Athens, Georgia;3. Department of Chemistry and Physics, Florida Gulf Coast University, Fort Myers, Florida;4. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina |
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Abstract: | Numerous genetic alterations have been identified during prostate cancer progression. The influence of environmental factors, particularly the diet, on the acceleration of tumor progression is largely unknown. Expression levels and/or activity of Src kinase are highly elevated in numerous cancers including advanced stages of prostate cancer. In this study, we demonstrate that high-fat diets (HFDs) promoted pathological transformation mediated by the synergy of Src and androgen receptor in vivo. Additionally, a diet high in saturated fat significantly enhanced proliferation of Src-mediated xenograft tumors in comparison with a diet high in unsaturated fat. The saturated fatty acid palmitate, a major constituent in a HFD, significantly upregulated the biosynthesis of palmitoyl-CoA in cancer cells in vitro and in xenograft tumors in vivo. The exogenous palmitate enhanced Src-dependent mitochondrial β-oxidation. Additionally, it elevated the amount of C16-ceramide and total saturated ceramides, increased the level of Src kinase localized in the cell membrane, and Src-mediated downstream signaling, such as the activation of mitogen-activated protein kinase and focal adhesion kinase. Our results uncover how the metabolism of dietary palmitate cooperates with elevated Src kinase in the acceleration of prostate tumor progression. |
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Keywords: | palmitate/fatty acid metabolism/Src kinase/prostate cancer |
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