title: K+channel signaling in irradiated tumor cells.
abstract: K+channels crosstalk with biochemical signaling cascades and regulate virtually all cellular processes by adjusting the intracellular K+concentration, generating the membrane potential, mediating cell volume changes, contributing to Ca2+signaling, and directly interacting within molecular complexes with membrane receptors and downstream effectors. Tumor cells exhibit aberrant expression and activity patterns of K+channels. The upregulation of highly "oncogenic" K+channels such as the Ca2+-activated IK channel may drive the neoplastic transformation, malignant progression, metastasis, or therapy resistance of tumor cells. In particular, ionizing radiation in doses used for fractionated radiotherapy in the clinic has been shown to activate K+channels. Radiogenic K+channel activity, in turn, contributes to the DNA damage response and promotes survival of the irradiated tumor cells. Tumor-specific overexpression of certain K+channel types together with the fact that pharmacological K+channel modulators are already in clinical use or well tolerated in clinical trials suggests that K+channel targeting alone or in combination with radiotherapy might become a promising new strategy of anti-cancer therapy. The present article aims to review our current knowledge on K+channel signaling in irradiated tumor cells. Moreover, it provides new data on molecular mechanisms of radiogenic K+channel activation and downstream signaling events.
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stegen
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.|Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Klumpp
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.
authors.forename: Milan
authors.initials: M
authors.lastname: Misovic
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Edalat
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.
authors.forename: Marita
authors.initials: M
authors.lastname: Eckert
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Klumpp
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Tübingen, Germany. stephan.huber@uni-tuebingen.de.
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D015221:Potassium Channels / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*
chemical_list: D015221:Potassium Channels
keywords: Ca2+ signalosome; Electrosignaling; Fractionated radiation therapy; Fura-2 Ca2+ imaging; Oncochannels; Patch-clamp recording