Cellular Signalling ( IF 4.8 ) Pub Date : 2018-07-07 , DOI: 10.1016/j.cellsig.2018.07.001 Wei Li , Xinfang Yu , Xiaolong Ma , Li Xie , Zhenkun Xia , Lijun Liu , Xinyou Yu , Jian Wang , Huiling Zhou , Xinmin Zhou , Yifeng Yang , Haidan Liu
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 β3. 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.
中文翻译:
Deguelin通过抑制CtsZ / FAK信号通路来减轻非小细胞肺癌细胞的转移
每年,肺癌都是男女癌症相关死亡的主要原因,这主要是由于转移引起的。尽管已经报道了天然化合物地精蛋白抑制各种癌细胞中的细胞迁移和侵袭,但是该调节进展的细节仍有待充分阐明。在这项研究中,我们调查了非小细胞肺癌(NSCLC)细胞的Deguelin抑制转移的潜在机制。我们的研究结果表明,在体外和体内,都柏林素均能抑制NSCLC细胞的迁移,侵袭和转移。通过抑制组织蛋白酶Z(CtsZ)的表达并中断CtsZ与整联蛋白β3的相互作用来介导deguelin的这些抑制作用。此外,deguelin抑制CtsZ下游FAK / Src / Paxillin信号传导的激活。击倒CtsZ模仿了deguelin对NSCLC细胞迁移和侵袭的影响。我们的研究表明,地精蛋白在体外和体内均发挥其抗转移作用,部分取决于CtsZ信号传导的抑制。Deguelin可能是针对NSCLC的潜在抗转移药。