Fig. 7.

A schematic diagram explaining how TRPC3 and NFATc1 signaling would regulate cell migration in MDA-MB-231. Long-term knockdown of TRPC3 (e.g. by lenti-shTRPC3) inhibits the Ca2 + entry across plasma membrane. This decrease in Ca2 + influx would in turn cause the translocation of NFATc1 from the nucleus to the cytosol and the NFATc1 signaling pathway would be inactivated concomitantly. When NFATc1 is activated, it would bind to the promoter of GPC6 and positively affect its expression. Due to the translocation of NFATc1 to the cytosol, nuclear NFATc1 would decrease, leading to less GPC6 being transcribed and expressed. In MDA-MB-231, GPC6 proteins directly interact with vinculin (a component of FAs) and regulate the actin cytoskeleton organization and the dynamics of FAs turnover. These would in turn determine cell migration. Long-term knockdown of GPC6 decreases migration of MDA-MB-231. Our study highlights a key functional role of the TRPC3-NFATc1-GPC6-vinculin signaling cascade in maintaining the migration of TNBC cells