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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.