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.
Oncogene. 2018 Mar 08 [Epub ahead of print]
Yan Cheng, Xing-Hua Gao, Xian-Jing Li, Qiu-Hua Cao, Dan-Dan Zhao, Jin-Rong Zhou, Hong-Xi Wu, Yun Wang, Lin-Jun You, Hong-Bao Yang, Yun-Long He, Yong-Ren Li, Jin-Song Bian, Qing-Yi Zhu, Lutz Birnbaumer, Yong Yang
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China., Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02138, USA., Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore., Department of Urology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, 210029, China., Neurobiology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, 27709, USA. ., State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China. .