Journal article
MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions
Cancer cell, Vol.31(3), pp.368-382
03/13/2017
PMID: 28292438
Abstract
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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•MAOA is associated with prostate cancer metastasis in clinical specimens•MAOA promotes metastasis by activating the paracrine Shh-IL6-RANKL signaling•MAOA drives tumor-stromal cell interactions in a vicious-cycle manner•MAOA inhibitor treatment reduces metastasis and prolongs survival in mice
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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Details
- Title
- MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions
- Creators
- Jason Boyang Wu - Washington State University, Pharmaceutical Sciences, Department ofLijuan Yin - Sichuan UniversityChanghong Shi - Cedars-Sinai Medical CenterQinlong Li - Xijing HospitalPeng Duan - Cedars-Sinai Medical CenterJen-Ming Huang - Cedars-Sinai Medical CenterChunyan Liu - Cedars-Sinai Medical CenterFubo Wang - Cedars-Sinai Medical CenterMichael Lewis - Veterans Health AdministrationYang Wang - Department of Pathology, Changhai Hospital, the Secondary Military Medical University, Shanghai 200433, ChinaTzu-Ping Lin - National Yang Ming UniversityChin-Chen Pan - Taipei Veterans General HospitalEdwin M Posadas - Cedars-Sinai Medical CenterHaiyen E Zhau - Cedars-Sinai Medical CenterLeland W.K Chung - Cedars-Sinai Medical Center
- Publication Details
- Cancer cell, Vol.31(3), pp.368-382
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Publisher
- Elsevier Inc
- Identifiers
- 99900620489601842
- Language
- English
- Resource Type
- Journal article