H-ras transformation sensitizes volume-activated anion channels and increases migratory activity of NIH3T3 fibroblasts.
Research output: Contribution to journal › Journal article › peer-review
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 language | English |
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Journal | Pflügers Archiv: European Journal of Physiology |
Volume | 455 |
Issue number | 6 |
Pages (from-to) | 1055-62 |
Number of pages | 7 |
ISSN | 0031-6768 |
DOIs | |
Publication status | Published - 2008 |
Bibliographical note
Keywords Migration - Cell volume - Cl- channel - Ras oncogene
ID: 2920924