Silencing ZIC2 abrogates tumorigenesis and anoikis resistance of non-small cell lung cancer cells by inhibiting Src/FAK signaling.
Silencing ZIC2 abrogates tumorigenesis and anoikis resistance of non-small cell lung cancer cells by inhibiting Src/FAK signaling.
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沉默 ZIC2 通过抑制 Src/FAK 信号传导消除非小细胞肺癌细胞的肿瘤发生和失巢凋亡抵抗
DOI：
10.1016/j.omto.2021.05.008
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发表时间：
2021-09-24
期刊：
影响因子：
--
通讯作者：
Shi K
中科院分区：
文献类型：
--
作者：
Liu A;Xie H;Li R;Ren L;Yang B;Dai L;Lu W;Liu B;Ren D;Zhang X;Chen Q;Huang Y;Shi K
锌指蛋白（ZIC）家族的异常表达已被广泛报道有助于多种人类癌症的进展和转移。然而，ZIC 2在非小细胞肺癌（NSCLC）中的功能作用和潜在机制在很大程度上是未知的。在本研究中，分别使用qRT-PCR、蛋白质印迹和免疫组织化学评估ZIC 2表达。进行体内动物实验和体外功能测定以研究ZIC 2在NSCLC中的作用。进行荧光素酶测定和染色质免疫沉淀（ChIP）以探索参与ZIC 2在NSCLC中的作用的潜在靶标。在这里，我们报道了ZIC 2在NSCLC组织中上调，并且ZIC 2的高表达预测NSCLC患者的总体和无进展生存率更差。沉默ZIC 2抑制肿瘤发生并降低NSCLC细胞的失巢凋亡抗性。机械研究进一步揭示，沉默ZIC 2转录抑制Src表达和失活类固醇受体共激活因子/粘着斑激酶信号传导，这进一步减弱NSCLC细胞的失巢凋亡抗性。重要的是，我们的结果表明，在NSCLC患者中，循环肿瘤细胞（CTC）的数量与ZIC 2表达呈正相关。总的来说，我们的研究结果揭示了ZIC 2在NSCLC中的新机制，这将促进NSCLC抗肿瘤策略的发展。我们确定了ZIC 2在NSCLC中的致癌作用。沉默ZIC 2通过转录抑制Src/FAK信号传导消除非小细胞肺癌细胞（NSCLC）的肿瘤发生和失巢凋亡抗性。因此，ZIC 2可能是NSCLC早期诊断和抗肿瘤策略的潜在生物标志物。
Aberrant expression of the zinc finger protein (ZIC) family has been extensively reported to contribute to progression and metastasis in multiple human cancers. However, the functional roles and underlying mechanisms of ZIC2 in non-small cell lung cancer (NSCLC) are largely unknown. In this study, ZIC2 expression was evaluated using qRT-PCR, western blot, and immunohistochemistry, respectively. Animal experiments in vivo and functional assays in vitro were performed to investigate the role of ZIC2 in NSCLC. Luciferase assays and chromatin immunoprecipitation (ChIP) were carried out to explore the underlying target involved in the roles of ZIC2 in NSCLC. Here, we reported that ZIC2 was upregulated in NSCLC tissues, and high expression of ZIC2 predicted worse overall and progression-free survival of NSCLC patients. Silencing ZIC2 repressed tumorigenesis and reduced the anoikis resistance of NSCLC cells. Mechanical investigation further revealed that silencing ZIC2 transcriptionally inhibited Src expression and inactivated steroid receptor coactivator/focal adhesion kinase signaling, which further attenuated the anoikis resistance of NSCLC cells. Importantly, our results showed that the number of circulating tumor cells (CTCs) was positively correlated with ZIC2 expression in NSCLC patients. Collectively, our findings unravel a novel mechanism implicating ZIC2 in NSCLC, which will facilitate the development of anti-tumor strategies in NSCLC. We pinpointed the oncogenic role of ZIC2 in NSCLC. Silencing ZIC2 abrogates tumorigenesis and anoikis resistance of non-small cell lung carcinoma cells (NSCLCs) by transcriptionally inhibiting Src/FAK signaling. Summarily, ZIC2 may hold the potential biomarker for early diagnosis and anti-tumor strategy in NSCLC.
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影响因子：
18.4
作者：
Bhagwat AS;Vakoc CR
通讯作者：
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影响因子：
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影响因子：
7.3
作者：
Chan, David W.;Liu, Vincent W. S.;Ngan, Hextan Y. S.
通讯作者：
Ngan, Hextan Y. S.
DOI：
10.1073/pnas.97.8.4198
发表时间：
2000-04-11
影响因子：
11.1
作者：
Güre, AO;Stockert, E;Chen, YT
通讯作者：
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影响因子：
9.7
作者：
Chen, Jiarong;Liu, Aibin;Huang, Yanming
通讯作者：
Huang, Yanming