WITHDRAWN: LPCAT1 promotes castration resistant prostate cancer progression by increasing PAF release and mRNA synthesis
Oncotarget(2018)
Abstract
// Bin Xu 1, * , Yajun Cheng 1, * , Guopeng Yu 1, * , Wenzhi Li 1 , Xiang Wan 1 , Juan Zhou 1 and Zhong Wang 1 1 Department of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhong Wang, email: zhongwang2000@sina.com Keywords: LPCAT1; castration resistant prostate cancer (CRPC); Histone H4 palmitorylattion; PAF Received: November 22, 2017 Accepted: January 25, 2018 Epub: February 09, 2018 ABSTRACT Our previous study demonstrated that compared with primary prostate cancer (PCa), Lysophosphatidylcholine Acyltransferase1 (LPCAT1) was overexpressed in castration resistant prostate cancer (CRPC) and regulated by androgen through the Wnt-dependent signaling pathway. However, its role in the progression of CRPC remains unclear. The aim of the present study was to explore the roles of LPCAT1 on CRPC progression and the underlying molecular mechanism. It was found that LPCAT1 promoted to the progression of CRPC in terms of proliferation, invasion and migration in vitro and in vivo . The decreased invasion and migration of CRPC cells induced by LPCAT1 silencing could be reversed by platelet activating factor acetylhydrolase (PAF-AH) and PAFR antagonist ABT-491, while the increased invasion and migration of CRPC cells induced by LPCAT1 overexpression can be reversed by exogenous PAF. However, the fluctuated ability of cell proliferation induced by LPCAT1 can’t be influenced by PAF-AH or exogenous PAF. Effect of LPCAT1 on increasing growth of CRPC cells by shifting into nucleus to palmitorylate Histone H4 in an androgen dependent-manner, thus enhancing mRNA synthesis. In addition, the increased expression of LPCAT1 in CRPC cells impaired sensitivity of cancer cells to paclitaxel (PTX) treatment. These results suggest that LPCAT1 may be an effective therapeutic target for CRPC therapy, though more studies are required to deeply elucidate the mechanism underlying role of LPCAT1 in promoting the progression of CRPC.
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Key words
resistant prostate cancer,resistant prostate cancer progression,prostate cancer,lpcat1,mrna
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