Regulation of CD44 expression and focal adhesion by Golgi phosphatidylinositol 4-phosphate in breast cancer.
Regulation of CD44 expression and focal adhesion by Golgi phosphatidylinositol 4-phosphate in breast cancer.
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DOI：
10.1111/cas.12968
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发表时间：
2016-07
期刊：
影响因子：
5.7
通讯作者：
Takenawa T
中科院分区：
文献类型：
--
作者：
Ijuin T;Takeuchi Y;Shimono Y;Fukumoto M;Tokuda E;Takenawa T
CD 44是一种跨膜受体，以标准或变体形式表达，在肿瘤进展和转移中起关键作用。这种蛋白质调节乳腺癌细胞中的细胞粘附和迁移。我们以前报道过，磷脂酰肌醇-4-磷酸（PI（4）P）在高尔基体调节乳腺癌细胞系的细胞迁移和侵袭。在这项研究中，我们发现通过敲低PI（4）P磷酸酶SAC 1增加高尔基体的PI（4）P水平增加了标准CD 44、变体CD 44和ezrin/radixin磷酸化的表达，并增强了MCF 7和SK-BR-3细胞中由CD 44和ezrin/radixin介导的粘着斑的形成。相反，在高度侵袭性的MDA‐MB‐231细胞中，PI 4‐激酶IIIβ的敲低降低了这些因子。这些结果表明，SAC 1表达和PI（4）P在高尔基体是重要的肿瘤的进展和转移，是潜在的乳腺癌的预后指标。
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 PI(4)P at the Golgi are important in tumor progression and metastasis and are potential prognostic markers of breast cancers.