Integrin activation, focal adhesion maturation and tumor metastasis / 生理学报

ABSTRACT

Integrins are a large family of heterodimeric cell adhesion molecules composed of α and β subunits. Through interaction with their specific ligands, integrins mediate cell-cell and cell-extracellular matrix interactions. Via outside-in signaling, integrins can recruit cytoplasmic proteins to their intracellular domains and then cluster into supramolecular structures and trigger downstream signaling. Integrin activation is associated with a global conformation rearrangement from bent to extended in ectodomains and the separation of α and β subunit cytoplasmic domains. During cell migration, integrins regulate the focal adhesion dynamics and transmit forces between the extracellular matrix and the cell cytoskeleton. In tumor microenvironment, integrins on multiple kinds of cells could be activated, which modulates cell migration into tumor and contributes to angiogenesis and tumor metastasis. Here, we review the mechanism of integrin activation, dynamics of focal adhesions during cell migration and tumor metastasis.