Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway.
Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway.
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抑郁通过交感神经-cAMP-FAK信号通路促进前列腺癌侵袭和转移。
DOI：
10.1038/s41388-018-0177-4
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发表时间：
2018-05
期刊：
影响因子：
8
通讯作者：
Yang, Yong
中科院分区：
文献类型：
--
作者：
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
抑郁症会导致癌症进展，并导致不良的临床结果。然而，抑郁症和癌症结果的潜在机制尚不清楚。本研究通过对98例前列腺癌患者的调查，发现心理抑郁得分高的患者与肿瘤的侵袭转移有关。我们发现黏着斑激酶（FAK）在有转移特征和抑郁评分高的癌症患者中升高。FAK敲低完全阻断原位移植肿瘤中抑郁促进的肿瘤侵袭。在Hi-myc小鼠和抑郁症小鼠模型中，在前列腺组织中检测到交感神经激活。此外，我们发现FAK激活依赖于cAMP-PKA信号通路。我们的研究结果表明，交感神经FAK信号通路在前列腺癌患者的高度抑郁症的激活促进肿瘤的侵袭。我们认为，用普萘洛尔阻断β 2 AR或用PF 562 271抑制FAK活化可能是治疗浸润性前列腺癌抑郁患者的新策略。
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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影响因子：
168.9
作者：
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通讯作者：
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影响因子：
28.2
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11.2
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影响因子：
8
作者：
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影响因子：
8.2
作者：
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通讯作者：
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