Data from Bidirectional Cross-talk between MAOA and AR Promotes Hormone-Dependent and Castration-Resistant Prostate Cancer

• DOI: 10.1158/0008-5472.c.6513082.v1
• Publication Date: 2023-03-31T21:26:40Z
• Authors: Jing Wei; Lijuan Yin; Jingjing Li; Jing Wang; Tianjie Pu; Peng Duan; Tzu-Ping Lin; Allen C. Gao; Boyang Jason Wu
• Keywords: Enzalutamide; Monoamine oxidase A

<div>Abstract<p>Androgen receptor (AR) is the primary oncogenic driver of prostate cancer, including aggressive castration-resistant cancer (CRPC). The molecular mechanisms controlling AR activation in general and reactivation CRPC remain elusive. Here we report that monoamine oxidase A (MAOA), a mitochondrial enzyme degrades neurotransmitters dietary amines, reciprocally interacts with cancer. MAOA was induced by androgens through direct binding to novel intronic androgen response element <i>MAOA</i> gene, which turn promoted transcriptional activity via upregulation Shh/Gli-YAP1 signaling enhance nuclear YAP1–AR interactions. Silencing suppressed AR-mediated development growth, CRPC, mice. expression elevated positively associated YAP1 human CRPC. Finally, genetic or pharmacologic targeting enhanced growth-inhibition efficacy enzalutamide, darolutamide, apalutamide both androgen-dependent cells. Collectively, these findings identify characterize an MAOA–AR reciprocal regulatory circuit coamplified effects Moreover, they suggest cotargeting this complex may be viable therapeutic strategy treat CRPC.</p>Significance:<p>MAOA comprise positive feedback loop providing mechanistic rationale for combining inhibition AR-targeted therapies treatment.</p></div>