Intervention of the myristoyl-protein biosynthesis for the treatment of prostate cancer
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Epidemiological studies about the correlation of dietary fat intake and prostate cancer are very controversial. I hypothesize that metabolism of dietary saturated fatty acids (SFAs) contribute to elevated activity of oncogenic proteins, thereby tumor progression. This thesis analyzes the contribution of dietary SFAs to prostate cancer, and summarizes biosynthetic pathways of how metabolism of SFAs will lead to the elevated levels of myristoyl-proteins. The metabolic processes include that 1) exogenous FAs are transported into cells in a variety of pathways, or endogenous FAs are biosynthesized through De novo synthesis or lipid salvage pathways; 2) Biosynthesis of acyl-CoAs catalyzed by Acyl-CoA synthetase Long Chain Family proteins. Finally, a variety of small molecule compounds has been developed to target either the myristoyl-CoA or the Gly-peptide binding sites of N-myristoyltransferase (NMT) to inhibit myristoylation process. The pharmaceutical intervention of NMT activity could be developed as chemotherapeutic approach for the treatment of cancer progression.