Cell volume changing model during cell migration. Cell migration is thought to be modeled as a continuous cycle of protrusion of the migrating cell front and retraction of the trailing end. A) In the migrating edge, ion channels and transporters, such as NKCC1, cause ion influx leading to an osmotic gradient, which results in water flowing into the cell. B) TRP channels allow the influx of Ca2+, which activates ion channels in the trailing edge. TRPM7 and swelling-induced Cl− channels are also thought to activate signaling pathways, such as MAPK/ERK signaling and PI3K/Akt pathways, leading to alterations in gene expression which enhance glioma cell migration and invasion. C) In the rear-end of the cell body, activated ion channels, such as CLC-3 and KCa3.1, induce ion and water efflux that causes cell shrinking only in the trailing end and results in cell retraction.