Kv10.1 K(+) channel: from physiology to cancer.

ABSTRACT

K(+) ions play a major role in many cellular processes. The deregulation of K(+) signaling is associated with a variety of diseases including cancer. Ether-à-go-go-1 (Eag1, Kv10.1, KCNH1) is a member of the voltage-activated potassium channel family and was the first K(+) channel to be associated with oncogenesis and tumor development. Interestingly, in healthy tissue, Kv10.1 is only detected in the central nervous system, where it is involved in the regulation of excitability under repeated stimulation. Kv10.1 is in contrast robustly expressed in over 70 % human tumors, where its expression seems to be controlled by key regulators of proliferation and survival such as p53 and E2F1, often altered in cancer. Otherwise, Kv10.1 is involved in cell proliferation, survival, angiogenesis, migration, and invasion. This review aims to provide a comprehensive overview of the current status of research on the role of Kv10.1 channel in physiopathology. Focus is placed on biophysical and pharmacological properties of Kv10.1 channel, as well as its cycling, trafficking, and its role in the neuron and cancer. The possible mechanisms by which Kv10.1 channel affects tumor cell migration and survival in breast cancer and its regulation by extracellular proteins are discussed.