title: Androgens promote prostate cancer cell growth through induction of autophagy.
abstract: 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.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Han
authors.forename: Jayantha B
authors.initials: JB
authors.lastname: Tennakoon
authors.forename: Fabiola F
authors.initials: FF
authors.lastname: Mehta
authors.forename: Fatima A
authors.initials: FA
authors.lastname: Merchant
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Howe
authors.forename: Donald P
authors.initials: DP
authors.lastname: McDonnell
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Frigo
mesh_terms: D000728:Androgens / Q000378:metabolism*; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D050155:Lipogenesis; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000728:Androgens; D008055:Lipids; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species