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

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.

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Acknowledgements

We thank Mrs. Ning Su for IHC studies, Mrs. Jian-hua Ding for HPLC studies, and Dr. Wen-tao Liu for gelatin zymography experiments and helpful suggestions. This study was supported by grants from Intramural Research Program of the NIH (Z01-ES101684 to LB), The 111 Project (No.111-2-07), National Science Foundation of China (91529304, 81673468 to YY, 81603132 to XG and 81403020 to LY), Natural Science Foundation of Jiangsu Province (No. BK20160753 to XG), and China Postdoctoral Science Foundation (No. 2016M591965 to XG).

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Correspondence to Lutz Birnbaumer or Yong Yang.

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