UM
Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression
Blessing, Alicia M.; Rajapakshe, Kimal; Bollu, Lakshmi Reddy; Shi, Yan; White, Mark A.; Pham, Alexander H.; Lin, Chenchu; Jonsson, Philip; Cortes, Constanza J.; Cheung, Edwin; La Spada, Albert R.; Bast, Robert C., Jr.; Merchant, Fatima A.; Coarfa, Cristian; Frigo, Daniel E.
2017
Source PublicationAUTOPHAGY
ISSN1554-8627
Volume13Issue:3Pages:506-521
AbstractAR (androgen receptor) signaling is crucial for the development and maintenance of the prostate as well as the initiation and progression of prostate cancer. Despite the AR's central role in prostate cancer progression, it is still unclear which AR-mediated processes drive the disease. Here, we identified 4 core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of AR in prostate cancer. These findings were significant in light of our recent observation that androgens promoted prostate cancer cell growth in part through the induction of autophagy. Expression of these 5 genes was essential for maximal androgen-mediated autophagy and cell proliferation. In addition, expression of each of these 5 genes alone or in combination was sufficient to increase prostate cancer cell growth independent of AR activity. Further, bioinformatic analysis demonstrated that the expression of these genes correlated with disease progression in 3 separate clinical cohorts. Collectively, these findings demonstrate a functional role for increased autophagy in prostate cancer progression, provide a mechanism for how autophagy is augmented, and highlight the potential of targeting this process for the treatment of advanced prostate cancer.
Keywordandrogen androgen receptor (AR) ATG4B ATG4D autophagy nuclear receptor prostate cancer TFEB ULK1 ULK2
DOI10.1080/15548627.2016.1268300
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000396845900006
PublisherTAYLOR & FRANCIS INC
The Source to ArticleWOS
Fulltext Access
Citation statistics
Cited Times [WOS]:49   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Blessing, Alicia M.,Rajapakshe, Kimal,Bollu, Lakshmi Reddy,et al. Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression[J]. AUTOPHAGY,2017,13(3):506-521.
APA Blessing, Alicia M..,Rajapakshe, Kimal.,Bollu, Lakshmi Reddy.,Shi, Yan.,White, Mark A..,...&Frigo, Daniel E..(2017).Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression.AUTOPHAGY,13(3),506-521.
MLA Blessing, Alicia M.,et al."Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression".AUTOPHAGY 13.3(2017):506-521.
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