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Regulation of CD44 expression and focal adhesion by Golgi phosphatidylinositol 4‐phosphate in breast cancer

机译:高尔基磷脂酰肌醇4-磷酸对乳腺癌CD44表达和粘着斑的调控

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摘要

CD44, a transmembrane receptor, is expressed in the standard or variant form and plays a critical role in tumor progression and metastasis. This protein regulates cell adhesion and migration in breast cancer cells. We previously reported that phosphatidylinositol‐4‐phosphate (PI(4)P) at the Golgi regulates cell migration and invasion in breast cancer cell lines. In this study, we showed that an increase in PI(4)P levels at the Golgi by knockdown of PI(4)P phosphatase SAC1 increased the expression of standard CD44, variant CD44, and ezrin/radixin phosphorylation and enhanced the formation of focal adhesions mediated by CD44 and ezrin/radixin in MCF7 and SK‐BR‐3 cells. In contrast, knockdown of PI 4‐kinase IIIβ in highly invasive MDA‐MB‐231 cells decreased these factors. These results suggest that SAC1 expression and style="fixed-case">PI(4)P at the Golgi are important in tumor progression and metastasis and are potential prognostic markers of breast cancers.
机译:CD44,一种跨膜受体,以标准或变异形式表达,在肿瘤的进展和转移中起关键作用。该蛋白调节乳腺癌细胞中的细胞粘附和迁移。我们先前曾报道高尔基体中的磷脂酰肌醇-4-磷酸酯(PI(4)P)调节乳腺癌细胞系中的细胞迁移和侵袭。在这项研究中,我们表明通过敲低PI(4)P磷酸酶SAC1可以增加高尔基体中PI(4)P的水平,从而增加标准CD44,变体CD44和ezrin / radixin磷酸化的表达,并增强局灶性形成CD44和ezrin / radixin介导的MCF7和SK‐BR‐3细胞粘附性。相反,在高侵袭性MDA-MB-231细胞中敲低PI 4激酶IIIβ可降低这些因素。这些结果表明,高尔基体上的SAC1表达和 style =“ fixed-case”> PI (4)P在肿瘤进展和转移中很重要,并且是乳腺癌的潜在预后标志物。

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