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HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer.
Zhu, Shimiao; Yang, Zhao; Zhang, Zheng; Zhang, Hongli; Li, Songyang; Wu, Tao; Chen, Xuanrong; Guo, Jianing; Wang, Aixiang; Tian, Hao; Yu, Jianpeng; Zhang, Changwen; Su, Lei; Shang, Zhiqun; Quan, Changyi; Niu, Yuanjie.
Afiliación
  • Zhu S; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Yang Z; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Zhang Z; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Zhang H; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Li S; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Wu T; Department of Urology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
  • Chen X; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Guo J; Department of Pathology, The Second Hospital of Tianjin Medical University, Tianjin, China.
  • Wang A; Institute of Urology, Peking University; National Urological Cancer Center, Beijing, China.
  • Tian H; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Yu J; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Zhang C; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China.
  • Su L; Department of Urology, People's Hospital of Rizhao, Rizhao, Shandong, China.
  • Shang Z; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China. zhiqun_shang@tmu.edu.cn.
  • Quan C; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China. quancahngyi@tmu.edu.cn.
  • Niu Y; Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Meidical University, Tianjin, 300211, China. niuyuanjie9317@163.com.
Cell Death Dis ; 14(3): 215, 2023 03 27.
Article en En | MEDLINE | ID: mdl-36973255
Enabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC. In vivo, upregulated HOXB3 contributed to CRPC xenografts progression and abiraterone resistance. To uncover the mechanism of HOXB3 driving tumor progression, we performed RNA-sequencing in HOXB3 negative (HOXB3-) and HOXB3 high (HOXB3 + ) staining CRPC tumors and determined that HOXB3 activation was associated with the expression of WNT3A and enriched WNT pathway genes. Furthermore, extra WNT3A and APC deficiency led HOXB3 to be isolated from destruction-complex, translocated to nuclei, and then transcriptionally regulated multiple WNT pathway genes. What's more, we also observed that the suppression of HOXB3 could reduce cell proliferation in APC-downregulated CRPC cells and sensitize APC-deficient CRPC xenografts to abiraterone again. Together, our data indicated that HOXB3 served as a downstream transcription factor of WNT pathway and defined a subgroup of CRPC resistant to antiandrogen which would benefit from HOXB3-targeted therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Cell Death Dis Año: 2023 Tipo del documento: Article País de afiliación: China 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 Resistentes a la Castración Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Cell Death Dis Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido