Potassium channels in cancer cells: a tool to reprogram immortality (893.14)

Abstract

K+ channels are traditionally known for controlling a variety of cell functions including electrical excitability, secretion and contraction. However, recent investigations have revealed that several K+ channels can be expressed in cancer cells of different histogenesis, suggesting that K+ channels can play a fundamental role in proliferation and in cancer biology. Yet, very little is known about function of K+ channels in cancer.Our studies revealed for the first time that stimulation of K+ channels (e.g. Kv11 or Kv7) activity with selective agonists determined an irreversible inhibition of cell proliferation in different cancer cells by arresting the cell cycle in G0/G1‐phase. We have characterized a set of biochemical pathways linking K+ channels to inhibition of tumor markers (cyclin E2, AKT) or stimulation of tumor suppressor (p21; p16) activities. We concluded that stimulation of K+ channel activity can lead to activation of a cellular senescence program in cancer cells.Cellular senescence is widely recognized as a potent antineoplastic mechanism however, very little is known about the molecular cascade controlling this phenomenon. In addition, the role of ion channels in determining cellular senescence has never been investigated. Therefore, our finding provides novel evidence for K+ channel functions that stretch beyond their traditional roles. In addition, our data offer the prospect to design an antiproliferative strategy for cancer treatment by using K+ channels agonists