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

• Published in: Oncogene Vol. 37; no. 22; pp. 2953 - 2966
• Main Authors: Cheng, Yan, Gao, Xing-Hua, Li, Xian-Jing, Cao, Qiu-Hua, 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2018; Nature Publishing Group
• Subjects: 13/1; 13/109; 13/51; 14/19; 14/5; 38/77; 631/67/1059/602; 631/67/589/466; 64/110; 64/60; 82/80; Animal models; Animals; Apoptosis; Cancer invasiveness; Cell Biology; Cell Line, Tumor; Complications and side effects; Cyclic adenylic acid; Cyclic AMP; Cyclic AMP - metabolism; Depression - complications; Depression - genetics; Depression - metabolism; Depression, Mental; Development and progression; Focal adhesion kinase; Focal Adhesion Kinase 1 - genetics; Focal Adhesion Kinase 1 - metabolism; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Health aspects; Human Genetics; Humans; Internal Medicine; Invasiveness; Kinases; Male; Medicine; Medicine & Public Health; Mental depression; Metastases; Metastasis; Mice; Myc protein; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Oncology; Phosphorylation; Physiological aspects; Propranolol; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - psychology; Protein kinase A; Protein kinases; Risk factors; Signal Transduction; Transplantation; Tumors; Up-Regulation; United States; China
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-018-0177-4

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.