Abstract
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.
Highlights
Migration is a critical step in tumor invasion and metastasis and involves decreased cell adhesion, cytoskeleton remodeling, extracellular matrix degradation and protrusion formation
We showed that CD147 positively correlates with Rac1 activity, which contributes to the formation of lamellipodia and mesenchymal movement of hepatocellular carcinoma (HCC) cells [12]
Using a differential interference contrast (DIC) microscope, we observed that knockout of CD147 expression in K7721 cells significantly attenuated lamellipodia formation, and resulted in the formation of filopodial protrusions at the leading edge compared to SMMC-7721 cells (Fig. 1A)
Summary
Migration is a critical step in tumor invasion and metastasis and involves decreased cell adhesion, cytoskeleton remodeling, extracellular matrix degradation and protrusion formation. Focal adhesions (FAs) are macromolecular complexes formed by various junctional proteins. They are located at connecting sites for integrin-mediated cell matrix adhesion, and participate in cell adhesion, migration and survival [1,2]. CD147 plays important roles in cellular processes of adhesion, invasion, migration, and extracellular matrix degradation [7,8,9]. Our previous studies indicated that CD147 upregulates the activities of integrins a3b1 and a6b1, leading to cytoskeleton rearrangement and changes in cell morphology through the FAK-paxillin and FAK-PI3K-Ca2+ signaling pathways, and subsequently enhances invasion and metastasis [10,11]. The precise role of CD147 in the regulation of FA formation and subsequent cytoskeleton reorganization to promote invasion and metastasis is not well understood
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