Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan
Cancer Res. 2014 Jun 1;74(11):3054-66. doi: 10.1158/0008-5472.CAN-13-2441. Epub 2014 Apr 4.
Downregulation of cell-cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell-cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIβ, which generates PI(4)P in the Golgi apparatus, increased cell-cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4)P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4)P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the Golgi apparatus.
细胞-细胞黏附的下调和细胞迁移能力的上调在良性肿瘤向侵袭性癌症的转化中起着关键作用。在这项研究中，我们表明，乳腺癌细胞中高尔基体内的磷脂酰肌醇 4-磷酸[PI(4)P]水平的变化会影响细胞-细胞黏附以及癌细胞迁移/侵袭能力。减弱 SAC1 的表达（一种定位于高尔基体内的 PI(4)P 磷酸酶）会导致弱侵袭性细胞的细胞-细胞黏附降低和迁移增加。相比之下，沉默在高尔基体内生成 PI(4)P 的磷脂酰肌醇 4-激酶 IIIβ，会增加高侵袭性细胞的细胞-细胞黏附并降低侵袭性。此外，发现一种 PI(4)P 效应蛋白，高尔基磷蛋白 3，其参与生成这些表型的方式依赖于其与 PI(4)P 的结合能力。我们的研究结果为乳腺癌细胞的进展提供了一个新模型，其中进展受高尔基体内的 PI(4)P 水平控制。
