Open AccessMAOA-a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells
Author(s) -
Yi Lin,
Yi Chang,
Mel Campbell,
Tzu Ping Lin,
Chin Chen Pan,
Hsin Chen Lee,
Jean C. Shih,
Pei Ching Chang
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep46338
Subject(s) - autophagy , monoamine oxidase a , apoptosis , cancer research , biology , transcription factor , microbiology and biotechnology , gene silencing , prostate cancer , monoamine oxidase , cancer , enzyme , biochemistry , gene , genetics
Autophagy and apoptosis are two well-controlled mechanisms regulating cell fate. An understanding of decision-making between these two pathways is in its infancy. Monoamine oxidase A (MAOA) is a mitochondrial enzyme that is well-known in psychiatric research. Emerging reports showed that overexpression MAOA is associated with prostate cancer (PCa). Here, we show that MAOA is involved in mediating neuroendocrine differentiation of PCa cells, a feature associated with hormone-refractory PCa (HRPC), a lethal type of disease. Following recent reports showing that NED of PCa requires down-regulation of repressor element-1 silencing transcription factor (REST) and activation of autophagy; we observe that MAOA is a novel direct target gene of REST. Reactive oxygen species (ROS) produced by overexpressed MAOA plays an essential role in inhibiting apoptosis and activating autophagy in NED PCa cells. MAOA inhibitors significantly reduced NED and autophagy activation of PCa cells. Our results here show MAOA as a new decision-maker for activating autophagy and MAOA inhibitors may be useful as a potential therapy for neuroendocrine tumors.