PMID- 29988966
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 48
DP  - 2018 Jun 22
TI  - V-ATPase-dependent repression of androgen receptor in prostate cancer cells.
PG  - 28921-28934
LID - 10.18632/oncotarget.25641 [doi]
AB  - Prostate Cancer (PCa) is the most commonly diagnosed cancer and the third leading 
      cause of death for men in the United States. Suppression of androgen receptor 
      (AR) expression is a desirable mechanism to manage PCa. Our studies showed that 
      AR expression was reduced in LAPC4 and LNCaP PCa cell lines treated with 
      nanomolar concentrations of the V-ATPase inhibitor concanamycin A (CCA). This 
      treatment decreased PSA mRNA levels, indicative of reduced AR activity. 
      V-ATPase-dependent repression of AR expression was linked to defective 
      endo-lysosomal pH regulation and reduced AR expression at the transcriptional 
      level. CCA treatment increased the protein level and nuclear localization of the 
      alpha subunit of the transcription factor HIF-1 (HIF-1alpha) in PCa cells via 
      decreased hydroxylation and degradation of HIF-1alpha. The addition of iron (III) 
      citrate restored HIF-1alpha hydroxylation and decreased total HIF-1alpha levels in PCa 
      cells treated with CCA. Moreover, iron treatment partially rescued CCA-mediated 
      AR repression. Dimethyloxalylglycine (DMOG), which prevents HIF-1alpha degradation 
      independently of V-ATPase, also decreased AR levels, supporting our hypothesis 
      that HIF-1alpha serves as a downstream mediator in the V-ATPase-AR axis. We propose a 
      new V-ATPase-dependent mechanism to inhibit androgen receptor expression in 
      prostate cancer cells involving defective endosomal trafficking of iron and the 
      inhibition of HIF-1 alpha-subunit turnover.
FAU - Licon-Munoz, Yamhilette
AU  - Licon-Munoz Y
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, University 
      of New Mexico Health Sciences Center, Albuquerque, New Mexico, 87131, USA.
FAU - Fordyce, Colleen A
AU  - Fordyce CA
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, University 
      of New Mexico Health Sciences Center, Albuquerque, New Mexico, 87131, USA.
FAU - Hayek, Summer Raines
AU  - Hayek SR
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, University 
      of New Mexico Health Sciences Center, Albuquerque, New Mexico, 87131, USA.
FAU - Parra, Karlett J
AU  - Parra KJ
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, University 
      of New Mexico Health Sciences Center, Albuquerque, New Mexico, 87131, USA.
LA  - eng
GR  - P30 CA118100/CA/NCI NIH HHS/United States
GR  - R01 GM086495/GM/NIGMS NIH HHS/United States
GR  - R03 DA031666/DA/NIDA NIH HHS/United States
GR  - P20 GM103451/GM/NIGMS NIH HHS/United States
GR  - P20 RR016480/RR/NCRR NIH HHS/United States
PT  - Journal Article
DEP - 20180622
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
CIN - Oncotarget. 2018 Aug 7;9(61):31793-31794. PMID: 30159121
PMC - PMC6034745
OTO - NOTNLM
OT  - HIF-1alpha
OT  - V-ATPase
OT  - androgen receptor
OT  - concanamycin
OT  - prostate cancer
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2018/07/11 06:00
MHDA- 2018/07/11 06:01
PMCR- 2018/06/22
CRDT- 2018/07/11 06:00
PHST- 2018/01/11 00:00 [received]
PHST- 2018/06/04 00:00 [accepted]
PHST- 2018/07/11 06:00 [entrez]
PHST- 2018/07/11 06:00 [pubmed]
PHST- 2018/07/11 06:01 [medline]
PHST- 2018/06/22 00:00 [pmc-release]
AID - 25641 [pii]
AID - 10.18632/oncotarget.25641 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jun 22;9(48):28921-28934. doi: 10.18632/oncotarget.25641. 
      eCollection 2018 Jun 22.