Ijuin Takeshi, Takeuchi Yukiko, Shimono Yohei, Fukumoto Miki, Tokuda Emi, Takenawa Tadaomi
Division of Biochemistry, Kobe University Graduate School of Medicine, Kobe, Japan.
The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan.
Cancer Sci. 2016 Jul;107(7):981-90. doi: 10.1111/cas.12968. Epub 2016 Jun 24.
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.
CD44是一种跨膜受体，以标准形式或变体形式表达，在肿瘤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。我们之前报道过，高尔基体处的磷脂酰肌醇-4-磷酸（PI(4)P）调节乳腺癌细胞系中的细胞迁移和侵袭。在本研究中，我们发现通过敲低PI(4)P磷酸酶SAC1来提高高尔基体处的PI(4)P水平，可增加标准CD44、变体CD44的表达以及埃兹蛋白/根蛋白的磷酸化，并增强MCF7和SK-BR-3细胞中由CD44和埃兹蛋白/根蛋白介导的粘着斑的形成。相反，在高侵袭性的MDA-MB-231细胞中敲低PI 4-激酶IIIβ会降低这些因子。这些结果表明，高尔基体处的SAC1表达和PI(4)P在肿瘤进展和转移中很重要，并且是乳腺癌潜在的预后标志物。
