All cells of the human body are at least transiently able to move and this is of high physiological relevance. The generation of structural asymmetry is the cellular response to chemical or mechanical cues in the environment and initiates cell locomotion. Variations of the intracellular Ca2+ concentration have long been implicated in coordinating the different steps in migration: protrusion and adhesion at the front, traction and detachment at the rear part of the cell. Important regulators of the intracellular Ca2+ concentration are members of the transient receptor potential (TRP) family of ion channels. So far, the molecular identity of Ca2+ channels involved in cell migration has not been defined; interesting candidates are mechanosensitive TRP channels like the channel TRPC1. We analyzed the function of the TRPC1 channel in transformed renal epithelial cells (MDCK- F-cells) with ablation of TRPC1 by RNAi. TRPC1 expression was decreased to 30% as quantified by means of immunofluorescence and RT-PCR. In timelapse video microscopy we could show, that "knockdown" of TRPC1 leads to partial loss of cellular polarity. TRPC1-knockdown cells show protrusions in several directions, unpolarized migration paths and decreased mean square displacement. Moreover the cell area of these cells is greatly increased. Together our data indicate that cell polarity and thereby migration depends on the action of the mechanosensitive Ca2+ channel TRPC1.