Autocrine activity of BDNF induced by the STAT3 signaling pathway causes prolonged TrkB activation and promotes human non-small-cell lung cancer proliferation.
Autocrine activity of BDNF induced by the STAT3 signaling pathway causes prolonged TrkB activation and promotes human non-small-cell lung cancer proliferation.
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STAT3信号通路诱导的BDNF自分泌活性导致TrkB延长激活并促进人非小细胞肺癌增殖
DOI：
10.1038/srep30404
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发表时间：
2016-07-26
影响因子：
4.6
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Chen B;Liang Y;He Z;An Y;Zhao W;Wu J
脑源性神经营养因子（脑源性神经营养因子）是神经营养蛋白超家族的成员，与神经系统的病理生理学有关。最近的研究表明BDNF和/或其受体原肌球蛋白相关激酶B（Trk B）参与了前列腺癌、神经母细胞瘤、胰腺导管癌、肝细胞癌和肺癌等多种肿瘤的生长和转移。尽管越来越重视BDNF/TrkB信号在人类肿瘤中的作用，但它如何参与原发性肿瘤尚未确定。此外，关于在非小细胞肺癌（NSCLC）进展中引发TrkB下游信号传导的分子机制知之甚少。在这项研究中，我们报告了BDNF在NSCLC样本中的显著表达，并表明BDNF刺激通过激活肺癌细胞中的STAT 3来增加BDNF本身的合成。BDNF的释放可以反过来激活TrkB信号传导。TrkB和STAT 3的激活都有助于下游信号传导并促进人非小细胞肺癌增殖。
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily, which has been implicated in the pathophysiology of the nervous system. Recently, several studies have suggested that BDNF and/or its receptor, tropomyosin related kinase B (TrkB), are involved in tumor growth and metastasis in several cancers, including prostate cancer, neuroblastoma, pancreatic ductal carcinoma, hepatocellular carcinoma and lung cancer. Despite the increasing emphasis on BDNF/TrkB signaling in human tumors, how it participates in primary tumors has not yet been determined. Additionally, little is known about the molecular mechanisms that elicit signaling downstream of TrkB in the progression of non-small-cell lung cancer (NSCLC). In this study, we report the significant expression of BDNF in NSCLC samples and show that BDNF stimulation increases the synthesis of BDNF itself through activation of STAT3 in lung cancer cells. The release of BDNF can in turn activate TrkB signaling. The activation of both TrkB and STAT3 contribute to downstream signaling and promote human non-small-cell lung cancer proliferation.