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热休克蛋白90α通过增强钙库操作性钙离子内流活性促进肝癌细胞转移 预览 被引量:1

eHsp90αpromotes hepatocellular carcinoma cell metastasis by enhancing SOCE activity
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摘要 目的探讨细胞外热休克蛋白90α(eHsp90α)对肝癌细胞转移的影响及机制。方法Western blot检测细胞培养基上清中eHsp90α的水平和细胞中基质相互作用分子1(STIM1)蛋白表达,Confocal检测钙库操作性钙离子内流(SOCE)活性,免疫荧光双染检测STIM1和ORAI1的相互作用水平,Transwell和划痕实验检测细胞转移能力。结果肝癌细胞系中eHsp90α较正常肝细胞系LO-2显著增加;高度转移能力的MHCC87H和HCCLM3细胞中eHsp90α水平、STIM1蛋白表达和SOCE活性较低转移能力的HepG2、HL-7702和SNU-449显著升高。hrHsp90α可以显著增加HepG2的转移能力、STIM1蛋白变化和SOCE活性。敲低STIM1蛋白表达或抑制SOCE活性,可以抑制MHCC87H的转移能力和hrHsp90α诱导的HepG2转移能力增加。结论eHsp90α可促进肝癌细胞的转移,其机制是通过诱导STIM1蛋白表达,进而增加SOCE活性。 Objective To investigate the effect and mechanism of extracellular heat shock protein 90α(eHsp90α)on the metastasis of hepatocellular carcinoma cells.Method The level of eHsp90αin the superna-tant of cell culture medium and stromal interaction molecule 1(STIM1)protein in the cells were detected by west-ern blot assay.The confocal assay was used to detect SOCE activity.Immunofluorescence double staining was used to detect the interaction between STIM1 and ORAI1.The transwell and wound-healing assay was performed to de-tect the metastasis of hepatocellular carcinoma cells.Results The expression of eHsp90αin hepatocellular carci-noma cell lines was significantly higher than that in normal liver cell line LO-2.The expression of eHsp90αand STIM1,and SOCE activity were significantly increased in MHC87H and HCCLM3 cells,with high metastatic abili-ty than that in HepG2,HL-7702 and SNU-449 cells.hrHsp90αcould significantly increase HepG2 metastasis,as well as STIM1 expression and SOCE activity.The metastasis of MHC87H cell and eHsp90α-induced HepG2 cell was inhibited when STIM1 was knockdown or SOCE activity was suppressed.Conclusion eHsp90αcan promote the metastasis of hepatocarcinoma cells by inducing STIM1 expression to increase SOCE activity.
作者 梁永红 冯超 周忠信 LIANG Yonghong;FENG Chao;ZHOU Zhongxin(Department of Vascular Surgery,The Third Affiliated Hospital of Southern Medical University,Guangzhou 510630,China)
出处 《实用医学杂志》 北大核心 2018年第23期3859-3864,共6页 The Journal of Practical Medicine
基金 广东省医学科学技术研究基金(编号:A2017561).
关键词 肝癌细胞 细胞外热休克蛋白90α 转移 钙库操作性钙离子内流 基质相互作用分子1 hepatocellular carcinoma cell extracellular Heat shock protein 90α metastasis store-operated calcium entry stromal interaction molecule 1
作者简介 通信作者:周忠信E?mail:1145364046@qq.com
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