Androgens regulate both the physiological development of the prostate and the pathology of prostatic diseases.
However, the mechanisms by which androgens exert their regulatory activities on these processes are poorly understood. In this study, we have determined that androgens regulate overall cell metabolism and cell growth, in part, by increasing autophagy in prostate cancer cells. Importantly, inhibition of autophagy using either pharmacological or molecular inhibitors significantly abrogated androgen-induced prostate cancer cell growth. Mechanistically, androgen-mediated autophagy appears to promote cell growth by augmenting intracellular lipid accumulation, an effect previously demonstrated to be necessary for prostate cancer cell growth. Further, autophagy and subsequent cell growth is potentiated, in part, by androgen-mediated increases in reactive oxygen species. These findings demonstrate a role for increased fat metabolism and autophagy in prostatic neoplasias and highlight the potential of targeting underexplored metabolic pathways for the development of novel therapeutics.
Written by:
Shi Y, Han JJ, Tennakoon JB, Mehta FF, Merchant FA, Burns AR, Howe MK, McDonnell DP, Frigo DE. Are you the author?
Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3605 Cullen Blvd, Houston, Texas 77204.
Reference: Mol Endocrinol. 2013 Feb;27(2):280-95
doi: 10.1210/me.2012-1260
PubMed Abstract
PMID: 23250485
