Activation of cell migration with fibroblast growth factor-2 requires calcium-sensitive potassium channels.
Tumor cell migration is crucial for the formation of tumor metastases and the progression of tumor disease. Fibroblast growth factor-2 (FGF-2) is one of the cytokines involved in the autocrine stimulation of tumor development. FGF-2 also stimulates transcription of Ca(2+)-sensitive K(+) channels (IK1 or K(Ca)3.1), which are part of the migration machinery in many cell types. Here, we tested whether FGF-2 acutely stimulates migration of transformed MDCK cells in a K(Ca)3.1 channel-dependent way. FGF-2 accelerates migration dose dependently. The speed of migration increases almost instantaneously. After 2 min, ERK1/2 phosphorylation has almost doubled. FGF-2 does not stimulate migration when ERK1/2 phosphorylation is inhibited. K(Ca)3.1 channel blockade also prevents the stimulatory effect of FGF-2 on cell migration. In addition, FGF-2 treatment leads to an activation of K(Ca)3.1 channels and a rapid rise of the cell area, which is because of an elevated rate of exocytosis. However, the amount of K(Ca)3.1 channels within the plasma membrane does not change. Our results show that there is a reciprocal interrelation between FGF-2 and K(Ca)3.1 channels. K(Ca)3.1 channels that are under the transcriptional control of FGF-2 are part of the FGF-2-mediated signaling cascade leading to an acceleration of migration.
Kessler
Wolfram
W
Klinik und Poliklinik für Allgemeine Chirurgie, Viszeral-, Thorax- und Gefässchirurgie, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
Budde
Thomas
T
Gekle
Michael
M
Fabian
Anke
A
Schwab
Albrecht
A
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1; D048049:Extracellular Signal-Regulated MAP Kinases