Abstract
BackgroundCell migration is a basic cellular behavior involved in multiple phenomena in the human body such as embryonic development, wound healing, immune reactions, and cancer metastasis. For proper cell migration, integrin and the ECM binding complex must be disassembled for the retraction of trailing edges.ObjectiveIntegrin must be differentially regulated at leading edges or trailing edges during cell migration. Previously, we showed that ITGBL1 was a secreted protein and inhibits integrin activity. Therefore, we examined the function of ITGBL1 on the retraction of trailing edges during cell migration.MethodsTo examined the function of ITGBL1 on cell migration, we knocked-down or overexpressed ITGBL1 by using ITGBL1 siRNA or ITGBL1 plasmid DNA in human chondrocytes or ATDC5 cells. We then characterized cellular migration and directionality by performing wound healing assays. Also, to analyze leading-edge formation and trailing-edge retraction, we labeled cell membranes with membrane-GFP and performed live imaging of migrating cells and. Finally, we specifically detected active forms of integrin, FAK and Vinculin using specific antibodies upon ITGBL1 depletion or overexpression.ResultIn this study, ITGBL1 preferentially inhibited integrin activity at the trailing edges to promote cell migration. ITGBL1-depleted cells showed increased focal adhesions at the membranous traces of trailing edges to prevent the retraction of trailing edges. In contrast, overexpression of ITGBL1 upregulated directional cell migration by promoting focal adhesion disassembly at the trailing edges.ConclusionITGBL1 facilitates directional cell migration by promoting disassembly of the trailing edge focal adhesion complex.
Highlights
Cell migration is cellular movement toward or away from specific signals and is a basic process of various cell types during embryonic development, wound healing for tissue repair, immune reactions, and even cancer cell metastasis (Friedl and Gilmour 2009; Ridley et al 2003)
Overexpression of ITGBL1 promoted trailing edge retraction and enhanced cell migration and directionality. These findings suggested that ITGBL1 preferentially inhibited the integrin-extracellular matrix (ECM) interaction at the trailing edges and promoted cell migration by facilitating trailing edge retractions
Integrin is critical for cell migration and mediates cell-ECM interactions
Summary
Cell migration is cellular movement toward or away from specific signals and is a basic process of various cell types during embryonic development, wound healing for tissue repair, immune reactions, and even cancer cell metastasis (Friedl and Gilmour 2009; Ridley et al 2003). Genes & Genomics migration is initiated in response to specific signals such as secreted proteins, chemicals, or mechanical signals Cells extend their leading edges using lamellipodia, which provide traction and contractile forces by binding to the extracellular matrix (ECM) to form a focal adhesion complex for cell migration. Cell migration is a basic cellular behavior involved in multiple phenomena in the human body such as embryonic development, wound healing, immune reactions, and cancer metastasis. Integrin and the ECM binding complex must be disassembled for the retraction of trailing edges. Overexpression of ITGBL1 upregulated directional cell migration by promoting focal adhesion disassembly at the trailing edges. Conclusion ITGBL1 facilitates directional cell migration by promoting disassembly of the trailing edge focal adhesion complex
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