Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway

• Autores: Cheng, Yan; Xing-Hua, Gao; Li, Xian-Jing; Cao, Qiuhua; Zhao, Dan-Dan; Zhou, Jin-Rong; Wu, Hong-Xi; Wang, Yun; You, Lin-Jun; Yang, Hong-Bao; He, Yun Long; Li, Yong-Ren; Bian, Jin-Song; Zhu, Qing-Yi; Birnbaumer, Lutz; Yang, Yong
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Oncogene. 2018, 37
• Materia: CANCER; DEPRESION; METASTASIS; TRATAMIENTO MEDICO
• Institución: Pontificia Universidad Católica Argentina

Fil: Cheng, Yan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Xing-Hua, Gao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Li, Xian-Jing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Cao, Qiu-Hua. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Zhao, Dan-Dan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Zhou, Jin-Rong. Harvard Medical School. Beth Israel Deaconess Medical Center. Department of Surgery. Nutrition/Metabolism Laboratory; Estados Unidos
Fil: Wu, Hong-Xi. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Wang, Yun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: You, Lin-Jun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Yang, Hong-Bao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: He, Yun-Long. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Li, Yong-Ren. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Fil: Bian, Jin-Song. National University of Singapore. Yong Loo Lin School of Medicine. Department of Pharmacology; Singapur
Fil: Zhu, Qing-Yi. Jiangsu Province Hospital of Traditional Chinese Medicine. Department of Urology; China
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research. State Key Laboratory of Natural Medicines. Key Laboratory of Drug Discovery for Metabolic Disease; China
Abstract: Depression drives cancer progression and induces poor clinical outcome. However, the mechanisms underlying depression and cancer outcomes are unclear. In this work, we investigated 98 prostate cancer patients and found that patients with high score of psychological depression were correlated with tumor invasion and metastasis. We found focal adhesion kinase (FAK) was increased in cancer patients with metastatic features and high score of depression. FAK knockdown completely blocked depression-promoted tumor invasion in orthotopic transplantation tumors. In Hi-myc mice and a murine model of depression, sympathetic activation was detected in the prostate tissue. Further we showed that FAK activation was dependent on a cAMP-PKA signaling pathway. Our results demonstrated that the activation of a sympathetic-FAK signaling pathway in prostate cancer patients with high degrees of depression facilitates tumor invasion. We suggest that blocking β2AR with propranolol or inhibiting FAK activation with PF562 271 may be novel strategies for depressed patients with invasive prostate cancer.