Original Research ARTICLE
GABARAPL1 promotes AR+ prostate cancer growth by increasing FL-AR/AR-V transcription activity and nuclear translocation
- 1The Second Affiliated Hospital of Xinxiang Medical University, China
- 2Xinxiang Medical University, China
- 3Shenzhen Peking University Hong Kong University of Science and Technology Medical Center, China
The next generation Androgen receptor (AR)-targeted thera¬pies are now in widespread clinical use and prolong prostate cancer (CaP) patient survival. However, the therapies are not curative due to diverse range of resistance mechanisms. AR variants (AR-V), one major mechanism of resistance, has recently gained momentum. Here, we found that GABARAPL1 knockdown inhibits the growth of AR-positive LNCaP and CWR22rv1 CaP cells in vitro and in vivo, decreases AR/AR-V transcription activity and AR nuclear translocation. Pulldown assay shows that both of Full-length (FL)-AR and AR-V were able to interact with GABARAPL1, suggesting that GABARAPL1 may play its role through directly scaffolding AR. The further analysis from Oncomine database showed that negative correlation between GABARAPL1 expression and 5-years survival in CaP cases. Our findings have identified GABARAPL1 as critical regulator of FL-AR/AR-V, suggesting the potential benefit of targeting GABARAPL1 to treat AR-positive CaP that is resistant to next generation AR inhibitors.
Keywords: prostate cancer, androgen receptor, AR variants, GABARAPL1, androgen deprivation therapy
Received: 03 Apr 2019;
Accepted: 30 Oct 2019.
Copyright: © 2019 Su, Zhang, Liu, Chen and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Bing Su, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China, email@example.com
Dr. WEi Zhang, Shenzhen Peking University Hong Kong University of Science and Technology Medical Center, Shenzhen, 518000, China, firstname.lastname@example.org