Activation of BDNF/TrkB pathway promotes prostate cancer progression via induction of epithelial-mesenchymal transition and anoikis resistance
Activation of BDNF/TrkB pathway promotes prostate cancer progression via induction of epithelial-mesenchymal transition and anoikis resistance
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BDNF/TrkB 通路的激活通过诱导上皮间质转化和失巢凋亡抵抗促进前列腺癌进展
DOI：
10.1096/fj.201802159rrr
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发表时间：
2020-05-11
期刊：
影响因子：
4.8
通讯作者：
Xing, Yifei
中科院分区：
文献类型：
--
作者：
Li, Tao;Yu, Ying;Xing, Yifei
前列腺癌（Prostate cancer，PCa）是世界范围内最常见的男性恶性肿瘤之一，但其发生发展的分子机制尚不清楚。本研究旨在探讨脑源性神经营养因子/原肌球蛋白受体激酶B（brain-derived neurotrophic factor/tropomyosin receptor kinase，BDNF/Trk B）通路在前列腺癌发病中的作用。免疫组化结果显示，PCa组织中BDNF和TrkB均呈高表达，TrkB的高表达与PCa的淋巴结转移和临床分期密切相关。体外研究表明，在PCa细胞中用rhBDNF刺激或过表达TrkB促进细胞迁移、侵袭和抗失巢凋亡。TrkB的过表达也导致上皮间质转化（EMT）样细胞形态的转化，而RNA干扰介导的TrkB耗竭引起EMT逆转。进一步的研究表明，蛋白激酶B（AKT）负责BDNF/Trk B信号诱导的促迁移和促侵袭作用，EMT和抗失巢凋亡。最后，体内研究证实，增强的TrkB表达促进肿瘤生长，而下调TrkB抑制肿瘤生长。我们的研究结果表明，BDNF/TrkB通路在PCa的进展中起重要作用，这可能为晚期PCa的治疗提供一种新的策略。
Prostate cancer (PCa) is one of the most common malignant diseases in male worldwide, yet, the molecular mechanisms involved in PCa progression are still poorly understood. This study aimed to investigate the roles of the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in PCa progression. It was demonstrated by immunohistochemical analysis that both BDNF and TrkB were overexpressed in PCa tissues and elevated TrkB expression was tightly related with lymph node metastasis and advanced stage of PCa. In vitro studies showed that stimulation with rhBDNF or overexpression of TrkB in PCa cells promoted cell migration, invasion, and anoikis resistance. Overexpression of TrkB also resulted in epithelial-mesenchymal transition (EMT)-like transformation in cell morphology, whereas RNA interference-mediated TrkB depletion caused reversion of EMT. Further investigation demonstrated that protein kinase B (AKT) was responsible for BDNF/TrkB signaling-induced pro-migratory and pro-invasive effects, EMT, and anoikis resistance. Finally, in vivo studies confirmed that enhanced TrkB expression facilitated tumor growth, whereas downregulation of TrkB suppressed tumor growth. Our findings illustrate that BDNF/TrkB pathway is crucial for PCa progression, which may provide a novel therapeutic strategy for the treatment of advanced PCa.