MTA1-TJP1 interaction and its involvement in non-small cell lung cancer metastasis.
MTA1-TJP1 interaction and its involvement in non-small cell lung cancer metastasis.
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MTA1-TJP1相互作用及其参与非小细胞肺癌转移
DOI：
10.1016/j.tranon.2022.101500
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发表时间：
2022-11
影响因子：
5
通讯作者：
Ye, Lianhua
中科院分区：
文献类型：
--
作者：
Wang, Wei;Ma, Mingsheng;Li, Li;Huang, Yunchao;Zhao, Guangqiang;Zhou, Yongchun;Yang, Yantao;Yang, Yichen;Wang, Biying;Ye, Lianhua
MTA1 was highly expressed in NSCLC tissues and was associated with tumor progression. MTA1 promoted NSCLC cell invasion and migration in vitro and in vivo. TJP1 was found to be an interacting protein of MTA1 involved in cell adhesion. MTA1 promoted NSCLC invasion and metastasis by inhibiting TJP1 protein expression and attenuating intercellular tight junctions. Targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis. Distant metastasis is the main cause of death in non-small cell lung cancer (NSCLC) patients. The mechanism of metastasis-associated protein 1(MTA1) in NSCLC has not been fully elucidated. This study aimed to reveal the mechanism of MTA1 in the invasion and metastasis of NSCLC. Bioinformatics analysis and our previous results showed that MTA1 was highly expressed in NSCLC tissues and correlated with tumor progression. Knockout of MTA1 by CRISPR/Cas9 significantly inhibited the migration and invasion of H1299 cells, but enhanced cell adhesion. Stable overexpression of MTA1 by lentivirus transfection had opposite effects on migration, invasion and adhesion of A549 cells. The results of in vivo experiments in nude mouse lung metastases model confirmed the promotion of MTA1 on invasion and migration. Tight junction protein 1 (TJP1) was identified by immunoprecipitation and mass spectrometry as an interacting protein of MTA1 involved in cell adhesion. MTA1 inhibited the expression level of TJP1 protein and weakened the tight junctions between cells. More importantly, the rescue assays confirmed that the regulation of MTA1 on cell adhesion, migration and invasion was partially attenuated by TJP1. In Conclusion, MTA1 inhibits the expression level of TJP1 protein co-localized in the cytoplasm and membrane of NSCLC cells, weakens the tight junctions between cells, and changes the adhesion, migration and invasion capabilities of cells, which may be the mechanism of MTA1 promoting the invasion and metastasis of NSCLC. Thus, targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis.
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影响因子：
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作者：
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通讯作者：
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