Androgens and the Lipogenic Switch in Prostate Cancer
Androgens have a major impact on prostate cancer cell biology and modulate a variety of key cellular processes and functions. One of the processes that are most strikingly affected is lipid biosynthesis. Through a unique indirect mechanism that involves activation of the lipogenic transcription factor SREBP, androgens coordinately stimulate the expression of more than 20 enzymes involved in lipid synthesis, and in this way they affect the entire lipogenic program in prostate cancer cells. Through additional mechanisms, including the stimulation of an ubiquitin-specific protease that removes the degradation-tag ubiquitin from lipogenic enzymes such as fatty acid synthase, an even more complex network of regulatory control is created. Progressive deregulation of this network results in a marked overexpression of lipogenic enzymes, referred to as the lipogenic switch. This switch typically accompanies the development and progression of prostate cancer and is thought to play an active role in prostate cancer cell biology. In fact, interference with the lipogenic process impairs proper membrane formation and functioning, halts cell proliferation, and induces cell death selectively in cancer cells. These findings suggest that enhanced lipogenesis in cancer cells is an essential trait of prostate cancer progression and is a promising novel target for antineoplastic intervention.
KeywordsAndrogen Receptor Prostate Cancer Cell Fatty Acid Synthesis Lipogenic Enzyme Induce Growth Arrest
The authors are supported by a grant “Concerted Research Action” by the K.U. Leuven and by research grants from the Research Foundation-Flanders (FWO) (Belgium). K. Brusselmans is a postdoctoral fellow of the Research Foundation-Flanders (FWO) (Belgium).
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