Artículos de revistas
Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway
Fecha
2018Registro en:
0950-9232 (impreso)
1476-5594 (en línea)
10.1038/s41388-018-0177-4
29515233
Autor
Cheng, Yan
Xing-Hua, Gao
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
Institución
Resumen
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.