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PP4R1 通过激活 MAPK/ERK 诱导的上皮-间充质转化促进非小细胞肺癌迁移和转移与 HMGA2 相互作用。

PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition.

机构信息

Department of Thoracic Surgery, The Affiliated Huadong Hospital of Fudan University, Shanghai, China.

Department of Respiration, The Affiliated Huadong Hospital of Fudan University, Shanghai, China.

出版信息

Mol Carcinog. 2020 May;59(5):467-477. doi: 10.1002/mc.23168. Epub 2020 Feb 19.

Abstract

Protein phosphatase 4 regulatory subunit 1 (PP4R1) has been shown to play a role in the regulation of centrosome maturation, apoptosis, DNA repair, and tumor necrosis factor signaling. However, the function of PP4R1 in non-small-cell lung cancer remains unclear. In this study, we identify PP4R1 as an oncogene through Oncomine database mining and immunohistochemical staining, and we showed that PP4R1 is upregulated in lung cancer tissues as compared with that in normal lung tissues and correlated with a poor prognosis in lung cancer patients. Furthermore, in vitro study by wound-healing and Transwell assay showed that PP4R1 could promote migration and invasion of lung cancer cells. Mechanistic investigations revealed that PP4R1 could cooperate with high mobility group AT-hook 2 and thereby promotes epithelial-mesenchymal transition via MAPK/extracellular receptor kinase activation. Taken together, our study provides a rich resource for understanding PP4R1 in lung cancer and indicates that PP4R1 may serve as a potential biomarker in lung cancer therapies.

摘要

蛋白磷酸酶 4 调节亚基 1(PP4R1)已被证明在调节中心体成熟、细胞凋亡、DNA 修复和肿瘤坏死因子信号转导中发挥作用。然而,PP4R1 在非小细胞肺癌中的功能尚不清楚。在这项研究中,我们通过 Oncomine 数据库挖掘和免疫组织化学染色鉴定 PP4R1 为癌基因,结果显示 PP4R1 在肺癌组织中上调,与肺癌患者的不良预后相关。此外,划痕愈合和 Transwell 分析的体外研究表明,PP4R1 可促进肺癌细胞的迁移和侵袭。机制研究表明,PP4R1 可以与高迁移率族 AT 钩 2 合作,从而通过 MAPK/细胞外受体激酶激活促进上皮-间充质转化。总之,我们的研究为理解 PP4R1 在肺癌中的作用提供了丰富的资源,并表明 PP4R1 可能成为肺癌治疗的潜在生物标志物。

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