info:eu-repo/semantics/article
Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway
Fecha
2018-03Registro en:
Cheng, Yan; Gao, Xing Hua; Li, Xian Jing; Cao, Qiu Hua; Zhao, Dan Dan; et al.; Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway; Nature Publishing Group; Oncogene; 37; 3-2018; 2953 - 2966
0950-9232
CONICET Digital
CONICET
Autor
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
Resumen
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.