Deguelin attenuates non-small cell lung cancer cell metastasis through inhibiting the CtsZ/FAK signaling pathway
Deguelin attenuates non-small cell lung cancer cell metastasis through inhibiting the CtsZ/FAK signaling pathway
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Deguelin 通过抑制 CtsZ/FAK 信号通路减弱非小细胞肺癌细胞转移
DOI：
10.1016/j.cellsig.2018.07.001
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发表时间：
2018-10-01
影响因子：
4.8
通讯作者：
Liu, Haidan
中科院分区：
文献类型：
--
作者：
Li, Wei;Yu, Xinfang;Liu, Haidan
肺癌是每年男性和女性癌症相关死亡的主要原因，主要是由于转移。虽然有报道称天然化合物deguelin可以抑制多种癌细胞的迁移和侵袭，但这种调控进展的细节仍有待充分阐明。在这项研究中，我们研究了去桂林抑制非小细胞肺癌（NSCLC）细胞转移的潜在机制。我们的研究结果表明，去圭林在体内和体外都能抑制非小细胞肺癌细胞的迁移、侵袭和转移。这些抑制作用是通过抑制组织蛋白酶Z （CtsZ）的表达和中断CtsZ与整合素β 3的相互作用来介导的。此外，去guelin抑制CtsZ下游FAK/Src/Paxillin信号的激活。CtsZ基因敲低可模拟去圭林对非小细胞肺癌细胞迁移和侵袭的影响。我们的研究表明，去圭林在体外和体内的抗转移作用部分依赖于对CtsZ信号的抑制。Deguelin可能是一种潜在的抗NSCLC转移药物。
Lung cancer is the leading cause of cancer-related death among both men and women every year, mainly due to metastasis. Although natural compound deguelin has been reported to inhibited cell migration and invasion in various cancer cells, the details of this regulation progress remain to be fully elucidated. In this study, we investigated the underlying mechanism of deguelin-suppressed metastasis of non-small cell lung cancer (NSCLC) cells. Our results demonstrate that deguelin inhibits NSCLC cell migration, invasion, and metastasis both in vitro and in vivo. These inhibitory effects of deguelin were mediated by suppressing of Cathepsin Z (CtsZ) expression and interrupting the interaction of CtsZ with integrin beta 3. Moreover, deguelin inhibits the activation of CtsZ downstream FAK/Src/Paxillin signaling. Knockdown of CtsZ mimicked the effect of deguelin on NSCLC cells migration and invasion. Our study reveals that deguelin exerts its anti-metastatic effect both in vitro and in vivo is partly dependent on the suppression of CtsZ signaling. Deguelin would be a potential anti-metastasis agent against NSCLC.