Staff – Department of Biology - University of Copenhagen

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H-ras transformation sensitizes volume-activated anion channels and increases migratory activity of NIH3T3 fibroblasts.

Research output: Research - peer-reviewJournal article

Linda Schneider, Thomas K Klausen, Christian Stock, Sabine Mally, Søren T Christensen, Stine Helene Falsig Petersen, Else K Hoffmann, Albrecht Schwab

The expression of the H-ras oncogene increases the migratory activity of many cell types and thereby contributes to the metastatic behavior of tumor cells. Other studies point to an involvement of volume-activated anion channels (VRAC) in (tumor) cell migration. In this paper, we tested whether VRACs are required for the stimulation of cell migration upon expression of the H-ras oncogene. We compared VRAC activation and migration of wild-type and H-ras-transformed NIH3T3 fibroblasts by means of patch-clamp techniques and time-lapse video microscopy. Both cell types achieve the same degree of VRAC activation upon maximal stimulation, induced by reducing extracellular osmolarity from 300 to 190 mOsm/l. However, upon physiologically relevant reductions in extracellular osmolarity (275 mOsm/l), the level of VRAC activation is almost three times higher in H-ras-transformed compared to wild-type fibroblasts. This increase in VRAC sensitivity is accompanied by increased migratory activity of H-ras fibroblasts. Moreover, the high-affinity VRAC blocker NS3728 inhibits migration of H-ras fibroblasts dose-dependently by up to about 60%, whereas migration of wild-type fibroblasts is reduced by only about 35%. Consistent with higher VRAC activity in H-ras than in wild-type fibroblasts, more VRAC blocker is needed to achieve a comparable degree of inhibition of migration. We suggest that H-ras modulates the volume set point of VRAC and thus facilitates transient changes of cell volume required for faster cell migration.
Original languageEnglish
JournalPflügers Archiv: European Journal of Physiology
Volume455
Issue number6
Pages (from-to)1055-62
Number of pages7
ISSN0031-6768
DOIs
StatePublished - 2008

Bibliographical note

Keywords Migration - Cell volume - Cl- channel - Ras oncogene

ID: 2920924