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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.

SUBMITTER: Cheng Y

PROVIDER: S-EPMC9637327 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Cheng Yan Y Gao Xing-Hua XH Li Xian-Jing XJ Cao Qiu-Hua QH Zhao Dan-Dan DD Zhou Jin-Rong JR Wu Hong-Xi HX Wang Yun Y You Lin-Jun LJ Yang Hong-Bao HB He Yun-Long YL Li Yong-Ren YR Bian Jin-Song JS Zhu Qing-Yi QY Birnbaumer Lutz L Yang Yong Y

Oncogene 20180308 22

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-pr ...[more]

PMID: 29515233

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

Publications

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

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