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Yin Yang 1 promotes the neuroendocrine differentiation of prostate cancer cells via the non-canonical WNT pathway (FYN/STAT3)

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机构： [1]Department of Urology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [2]Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. [3]Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. [4]Department of Urology, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China.

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关键词： cellular lineage plasticity EMT FZD8 neuroendocrine differentiation of prostate cancer YY1

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A growing number of studies have shown that Yin Yang 1 (YY1) promotes the development of multiple tumours. The purpose of the current study was to determine the mechanism by which YY1 mediates neuroendocrine differentiation of prostate cancer (NEPC) cells undergoing cellular plasticity.Using the Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, we bioinformatically analyzed YY1 expression in prostate cancer (PCa). Aberrant YY1 expression was validated in different PCa tissues and cell lines via quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. In vivo and in vitro functional assays verified the oncogenicity of YY1 in PCa. Further functional assays showed that ectopic expression of YY1 promoted cellular plasticity in PCa cells via epithelial-mesenchymal transition induction and neuroendocrine differentiation.Androgen deprivation therapy induced a decrease in YY1 protein ubiquitination, enhanced its stability, and thus enhanced the transcriptional activity of FZD8. Castration enhanced FZD8 binding to Wnt9A and mediated cellular plasticity by activating the non-canonical Wnt (FZD8/FYN/STAT3) pathway.We identified YY1 as a novel dysregulated transcription factor that plays an important role in NEPC progression in this study. We believe that an in-depth investigation of the mechanism underlying YY1-mediated disease may lead to improved NEPC therapies.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

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出版当年[2023]版：

大类 | 1 区医学

小类 | 2 区医学：研究与实验 2 区肿瘤学

最新[2023]版：

大类 | 1 区医学

小类 | 2 区医学：研究与实验 2 区肿瘤学

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出版当年[2023]版：

Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

最新[2023]版：

Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

影响因子： 7.9 最新[2023版] 8 最新五年平均 7.9 出版当年[2023版] 8 出版当年五年平均 10.6 出版前一年[2022版]

第一作者：

第一作者机构： [1]Department of Urology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [2]Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. [3]Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.

通讯作者：

通讯机构： [1]Department of Urology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [2]Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. [3]Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. [4]Department of Urology, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China. [*1]Department of Urology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. [*2]Department of Urology, Zhongda Hospital, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing 210009, China.

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Yin Yang 1 promotes the neuroendocrine differentiation of prostate cancer cells via the non-canonical WNT pathway (FYN/STAT3)

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