Role of Site-Specific Glycosylation in the I-Like Domain of Integrin ?1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation.

ABSTRACT: Integrin ?1 plays an essential role in the crosstalk between tumor cells and their microenvironment. Aberrant N-glycosylation of integrin ?1 was documented to alter integrin ?1 expression, dimerization, and biological function. However, the biological function of site-specific N-glycosylation of integrin ?1 on extracellular vesicles is not fully understood. In this study, we mutated putative N-glycosylation sites in different domains of integrin ?1. Removal of the N-glycosylation sites on the I-like domain of integrin ?1 (termed the ?4-6 ?1 mutant) suppressed focal adhesion kinase (FAK) signaling, cell migration, and adhesion compared with other ?1 mutants. Cell adhesion, migration, and activation of FAK were suppressed in recipient MCF7 cells co-cultured with ?4-6 mutant cells and treated with small extracellular vesicles (sEVs) from ?4-6 mutant cells. Notably, the wild-type and ?1 mutant were both present in sEVs, and could be transferred to recipient cells via sEVs, resulting in changes of cell behavior. Our findings demonstrate the important roles of N-glycosylation of the I-like domain of integrin ?1. Moreover, the vesicular ?4-6 ?1 mutant can regulate integrin-mediated functions in recipient cells via sEVs.

SUBMITTER: Cao L 

PROVIDER: S-EPMC7916680 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature