Fig. 7

Model of the ABCA1 activity influence on Hs294T cells motility and ECM degradation processes. A (1) ABCA1 activity influences the cholesterol distribution within Hs294T PM, creating a heterogeneous lipid packing where lipids and membrane proteins can diffuse actively. (2) This specific PM lateral organization leads to the formation of integrin αVβ3 clusters that elicit activation of integrin β3 and trigger stable docking of phosphorylated FAK at the FAs and migration of the cells. (3) The specific PM lateral orsganization also influences the formation of active invadopodia which in turn increases the ECM degradation. (4) The rise in migration and the ECM digestion finally enhances the melanoma cells’ invasion potential. B (1) Loss of ABCA1 expression or activity triggers the accumulation of cholesterol within the PM and its excess is transformed into esterified cholesterol in lipid droplets. The PM fluidity decreases as the lipid packing rises, making the PM more homogeneous. (2) The decrease of PM fluidity destabilizes the integrin αVβ3 (with active integrin β3) clusters formation and the retaining of phosphorylated FAK at FAs, thus inhibiting the motility of the cells. (3) Accumulation of cholesterol and alteration of the PM lateral organization also inhibit the active invadopodia formation, partially preventing the ECM degradation. (4) Combined decrease in cells migration and ECM degradation lowers melanoma cells’ metastatic potential