p120-catenin isoform 3 regulates subcellular localization of Kaiso and promotes invasion in lung cancer cells via a phosphorylation-dependent mechanism
p120-catenin isoform 3 regulates subcellular localization of Kaiso and promotes invasion in lung cancer cells via a phosphorylation-dependent mechanism
复制标题
p120-连环蛋白异构体 3 调节 Kaiso 的亚细胞定位，并通过磷酸化依赖性机制促进肺癌细胞的侵袭。
DOI：
10.3892/ijo.2011.995
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发表时间：
2011-06-01
影响因子：
5.2
通讯作者：
Wang, En-Hua
中科院分区：
文献类型：
--
作者：
Zhang, Peng-Xin;Wang, Yan;Wang, En-Hua
p120-catenin调节E-cadherin在质膜上的稳定性以及细胞质中Rho GTPase的活性，并与细胞核中的转录抑制因子Kaiso相互作用。然而，不同同工异构体的作用和p120-连环蛋白在细胞核中的磷酸化状态尚不清楚。在本研究中，我们通过免疫沉淀发现p120-连环蛋白异构体3在肺癌细胞中与Kaiso相互作用。核细胞质提取和免疫荧光证实Kaiso通过p120-连环蛋白异构体3从细胞核中穿梭出来。由于leptomycin抑制染色体区域维持依赖的核输出，p120-连环蛋白异构体3对Kaiso细胞质的富集被取消。肺肿瘤组织和细胞系表达较高水平的丝氨酸288磷酸化形式。此外，p120-catenin亚型3中丝氨酸288的磷酸化增强了与Kaiso的结合。此外，免疫荧光和transwell侵袭实验表明，p120-catenin丝氨酸和苏氨酸位点的磷酸化诱导F-actin重塑，促进肺癌细胞的侵袭。总之，我们的数据表明p120-连环蛋白异构体3通过磷酸化依赖机制调节Kaiso的核输出并促进肺癌细胞的侵袭。丝氨酸288磷酸化可促进肺癌的进展。
p120-catenin regulates E-cadherin stability at the plasma membrane as well as Rho GTPase activity in the cytoplasm, and also interacts with the transcriptional repressor, Kaiso, in the nucleus. However, the role of different isoforms and the phosphorylated state of p120-catenin in the nucleus is poorly understood. In the present study, we show that p120-catenin isoform 3 interacts with Kaiso in lung cancer cells by immunoprecipitation. Nuclear-cytoplasmic extraction and immunofluorescence confirmed that Kaiso shuttled out of the nucleus via p120-catenin isoform 3. The cytoplasmic enrichment of Kaiso by p120-catenin isoform 3 was abolished due to the inhibition of chromosomal region maintenance-dependent nuclear export via leptomycin. The lung tumor tissue and cell lines expressed higher levels of the serine 288 phosphorylated form. Also, serine 288 phosphorylation in p120-catenin isoform 3 enhanced the binding with Kaiso. Moreover, immunofluorescence and transwell invasion assay showed that the phosphorylation of serine and threonine sites in p120-catenin induced F-actin remodelling and promoted the invasion of lung cancer cells. Collectively, our data establish that p120-catenin isoform 3 regulates the nuclear export of Kaiso and promotes invasion in lung cancer cells via a phosphorylation-dependent mechanism. Serine 288 phosphorylation can contribute to lung cancer progression.