HAb18G/CD147 regulates vinculin-mediated focal adhesion and cytoskeleton organization in cultured human hepatocellular carcinoma cells.

HAb18G/CD147 regulates vinculin-mediated focal adhesion and cytoskeleton organization in cultured human hepatocellular carcinoma cells.
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HAb18G/CD147 调节培养的人肝细胞癌细胞中粘着蛋白介导的局部粘附和细胞骨架组织

DOI:
10.1371/journal.pone.0102496
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Chen ZN
Chen ZN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liang Q;Han Q;Huang W;Nan G;Xu BQ;Jiang JL;Chen ZN

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局灶黏附(FAs)是一种整合素介导的位于细胞膜外界面的大分子复合物,已被证明可以调节细胞的黏附和迁移。我们之前的研究表明,HAb18G/CD147 (CD147)参与人肝细胞癌(HCC)细胞骨架重组和FA形成。然而,这些过程背后的确切机制尚不清楚。在目前的研究中,我们确定CD147参与了肝细胞癌细胞中由白细胞素介导的FA局灶粘连形成。我们还发现,CD147的缺失导致了血管素介导的FA面积(P<0.0001)、长度/宽度比(P<0.0001)和平均强度(P<0.0001)的减少。CD147通过将Arp2/3定位到细胞边缘来促进板足的形成。CD147的缺失显著降低了vculin介导的局灶黏附的荧光(t1 /2)恢复时间(22.7±3.3 s) (P<0.0001)。在细胞扩散实验中,CD147被发现是动态黏附扩大和分解所必需的。此外,目前的数据显示,CD147减少了酪氨酸磷酸化在vinculin介导的局灶粘连中,并增强了酸性磷脂磷脂酰肌醇4,5 -二磷酸(PIP2)的积累。总之,这些结果表明CD147参与了白细胞素介导的局灶黏附形成,随后促进细胞骨架重组,促进人类HCC细胞的侵袭和迁移。
Focal adhesions (FAs), integrin-mediated macromolecular complexes located at the cell membrane extracellular interface, have been shown to regulate cell adhesion and migration. Our previous studies have indicated that HAb18G/CD147 (CD147) is involved in cytoskeleton reorganization and FA formation in human hepatocellular carcinoma (HCC) cells. However, the precise mechanisms underlying these processes remain unclear. In the current study, we determined that CD147 was involved in vinculin-mediated FA focal adhesion formation in HCC cells. We also found that deletion of CD147 led to reduced vinculin-mediated FA areas (P<0.0001), length/width ratios (P<0.0001), and mean intensities (P<0.0001). CD147 promoted lamellipodia formation by localizing Arp2/3 to the leading edge of the cell. Deletion of CD147 significantly reduced the fluorescence (t 1/2) recovery times (22.7±3.3 s) of vinculin-mediated focal adhesions (P<0.0001). In cell-spreading assays, CD147 was found to be essential for dynamic focal adhesion enlargement and disassembly. Furthermore, the current data showed that CD147 reduced tyrosine phosphorylation in vinculin-mediated focal adhesions, and enhanced the accumulation of the acidic phospholipid phosphatidylinositol-4, 5-bisphosphate (PIP2). Together, these results revealed that CD147 is involved in vinculin-mediated focal adhesion formation, which subsequently promotes cytoskeleton reorganization to facilitate invasion and migration of human HCC cells.
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