The protein hERG1, which functions to control the heart beat, is also associated with cancer metastasis. This is the result of the study "The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression"that is published in the journal Science Signaling. (Cusabio offers a number of proteins such as Recombinant IL4R.) The study, led by Annarosa Arcangeli and colleagues from the University of Firenze and researchers from several other institutions in Italy and Netherlands, reveals that "the interaction of β1 integrins with hERG1 channels in cancer cells stimulated distinct signaling pathways that depended on the conformational state of hERG1 and affected different aspects of tumor progression." Ion fluxes across cellular membranes have a significant impact on cellular homeostasis. Ion channels regulate many cellular processes including proliferation, differentiation, and migration through a family of transmembrane receptors called integrins. Integrins mediate attachment of cells to other cells or to the extracellular matrix, and an integrin molecule consists of an α subunit and a β subunit. Dysregulation of ion channels activity is implicated in many diseases, including cancer. However, the role of ion channels in cancer biology remains elusive. The hERG1 potassium channel is best known for its contribution to the electrical activity of the heart that coordinates the heart's beating. Accumulating evidence suggests that hERG1 potassium channels are overexpressed in various human cancers. In this work, the team focused on the interaction between hERG1 and the β1 integrin subunit. They demonstrated in immunodeficient mice that "metastasis of breast cancer cells was reduced when the hERG1/β1 integrin interaction was disrupted." This indicates that pharmacologic manipulation of the hERG1 in cancer cells might be a treatment strategy. The researchers hope that their findings would aid in the development of drugs that can selectively target hERG1 in tumors and have no negative effect on the heart function. Previous studies have shown that hERG1 blockage decreases tumor growth in animal models. But tumor therapies directed against hERG1 have potential cardiotoxicity, which discourages their use. Further investigation is needed to better elucidate the aberrant hERG1 expression in cancer. Findings in this field may have both diagnosis and therapy applications.
