MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions

Publication date: 13 March 2017
Source:Cancer Cell, Volume 31, Issue 3
Author(s): Jason Boyang Wu, Lijuan Yin, Changhong Shi, Qinlong Li, Peng Duan, Jen-Ming Huang, Chunyan Liu, Fubo Wang, Michael Lewis, Yang Wang, Tzu-Ping Lin, Chin-Chen Pan, Edwin M. Posadas, Haiyen E. Zhau, Leland W.K. Chung
Metastasis is a predominant cause of death for prostate cancer (PCa) patients; however, the underlying mechanisms are poorly understood. We report that monoamine oxidase A (MAOA) is a clinically and functionally important mediator of PCa bone and visceral metastases, activating paracrine Shh signaling in tumor-stromal interactions. MAOA provides tumor cell growth advantages in the bone microenvironment by stimulating interleukin-6 (IL6) release from osteoblasts, and triggers skeletal colonization by activating osteoclastogenesis through osteoblast production of RANKL and IL6. MAOA inhibitor treatment effectively reduces metastasis and prolongs mouse survival by disengaging the Shh-IL6-RANKL signaling network in stromal cells in the tumor microenvironment. These findings provide a rationale for targeting MAOA and its associated molecules to treat PCa metastasis.

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Teaser

Wu et al. show that monoamine oxidase A (MAOA) is an important mediator of prostate cancer bone and visceral metastases by activating paracrine Shh-IL6-RANKL signaling in tumor-stromal interactions. Pharmacological inhibition of MAOA restricts metastasis and extends survival in a mouse prostate cancer model.


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