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Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2.
Liu, Qiuli; Pang, Jian; Wang, Lin-Ang; Huang, Zhuowei; Xu, Jing; Yang, Xingxia; Xie, Qiubo; Huang, Yiqiang; Tang, Tang; Tong, Dali; Liu, Gaolei; Wang, Luofu; Zhang, Dianzheng; Ma, Qiang; Xiao, Hualiang; Lan, Weihua; Qin, Jun; Jiang, Jun.
Afiliación
  • Liu Q; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Pang J; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Wang LA; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Huang Z; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Xu J; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Yang X; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Xie Q; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Huang Y; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Tang T; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Tong D; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Liu G; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Wang L; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Zhang D; Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA.
  • Ma Q; Department of Pathology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Xiao H; Department of Pathology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Lan W; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Qin J; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
  • Jiang J; CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, PR China.
J Pathol ; 253(1): 106-118, 2021 01.
Article en En | MEDLINE | ID: mdl-33009820
Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient-derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Factores de Transcripción / Adenocarcinoma / Biomarcadores de Tumor / Carcinoma Neuroendocrino / Epigénesis Genética / Factor Nuclear 3-beta del Hepatocito / Histona Demetilasas Límite: Animals / Humans / Male Idioma: En Revista: J Pathol Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Factores de Transcripción / Adenocarcinoma / Biomarcadores de Tumor / Carcinoma Neuroendocrino / Epigénesis Genética / Factor Nuclear 3-beta del Hepatocito / Histona Demetilasas Límite: Animals / Humans / Male Idioma: En Revista: J Pathol Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido