2. Academic Validation
  3. Monoamine oxidase A drives neuroendocrine differentiation in prostate cancer

Monoamine oxidase A drives neuroendocrine differentiation in prostate cancer

  • Biochem Biophys Res Commun. 2022 May 28;606:135-141. doi: 10.1016/j.bbrc.2022.03.096.
Xue Shui 1,  Xuehua Ren 2,  Rong Xu 3,  Qinghua Xie 4,  Yaohua Hu 1,  Jing Qin 3,  Han Meng 3,  Caiqin Zhang 3,  Jumei Zhao 5,  Changhong Shi 6
Affiliations

Affiliations

  • 1 Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China; School of Basic Medical Sciences, Medical College of Yan'an University, 580 Bao-Ta Street, 716000, Yanan, China.
  • 2 Shaanxi Stem Cell Engineering and Technology Research Center, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China.
  • 3 Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
  • 4 Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China; Animal Experiment Center, Guangzhou University of Chinese Medicine, 510000, Guangzhou, Guangdong, China.
  • 5 School of Basic Medical Sciences, Medical College of Yan'an University, 580 Bao-Ta Street, 716000, Yanan, China. Electronic address: Ydzhjm@yau.edu.cn.
  • 6 Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China. Electronic address: changhong@fmmu.edu.cn.
PMID: 35349822 DOI: 10.1016/j.bbrc.2022.03.096
Abstract

Neuroendocrine transdifferentiation (NED) of prostate Cancer (PCa) is the main cause of failure of Androgen Receptor Inhibitor treatment. However, the molecular mechanisms underlying the development of NEPC, especially treatment-induced NEPC, remain unclear. Emerging evidence indicates that elevated Monoamine Oxidase A (MAOA) contribute to the proliferation, cell stemness, and bone metastasis in PCa. Here, we generated an enzalutamide-induced NED cell model to assess the role of MAOA during NED. Overall, MAOA expression was significantly increased upon Enz long-term exposure and was required for neuroendocrine marker expression. In particular, Enz was found to induce NED via the MAOA/mTOR/HIF-1α signaling axis. Further analyses revealed that the MAOA inhibitor clorgyline(CLG) may bring multiple benefits to CRPC patients, including better therapeutic effect and delays NED. These findings suggest that MAOA may be an important target for the development of anti-NED therapies, thereby providing a novel strategy for the combined application of CLG and AR inhibitors in the clinic.

Keywords

Monoamine oxidase A; Neuroendocrine differentiation; Prostate cancer.

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