Ion Channel Conformations Regulate Integrin-Dependent Signaling

Cell-matrix adhesion determines the choice between different cell fates and is accompanied by substantial changes in ion transport. The greatest evidence is the bidirectional interplay occurring between integrin receptors and K+ channels. These proteins can form signaling hubs that regulate cell proliferation, differentiation, and migration in normal and neoplastic tissue. Recent results show that the physical interaction with integrins determines the balance of the open and closed K+ channel states, and individual channel conformations regulate distinct downstream pathways. We propose a model of how these mechanisms regulate proliferation and metastasis in cancer cells. In particular, we suggest that the neoplastic progression could be modulated by targeting specific ion channel conformations. Integrin-mediated cell adhesion determines the choice between different cell fates and is intimately linked to the regulation of ion transport. Integrin receptors and ion channels form signaling hubs that recruit growth factor receptors and signaling proteins to regulate cell proliferation, differentiation, and migration. Ion channels regulate downstream pathways by conductive and nonconductive signals. Their association with integrins determines the balance of the open and closed channel conformations. We propose how the latter can regulate distinct intracellular pathways in normal and cancer cells. We suggest that individual stages of the neoplastic progression could be modulated by targeting specific macromolecular complexes or distinct ion channel conformations.