Integrin β-like 1 protein (ITGBL1) promotes cell migration by preferentially inhibiting integrin-ECM binding at the trailing edge

다국어 초록 (Multilingual Abstract)

Background: 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. For proper cell migration, integrin and the ECM binding complex must be disassembled for the retraction of trailing edges.
Objective: Integrin 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.
Methods: To 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.
Result: In 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.
Conclusion: ITGBL1 facilitates directional cell migration by promoting disassembly of the trailing edge focal adhesion complex.

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