Tumor cell migration is a crucial step in the metastatic cascade, and interruption of this step is considered to be logically effective in preventing tumor metastasis. Lipid rafts, distinct liquid ordered plasma membrane microdomains, have been shown to influence cancer cell migration, but the underlying mechanisms are still not well understood. Here, we report that lipid rafts regulate the dynamics of actin cytoskeleton and focal adhesion in human melanoma cell migration. Disrupting the integrity of lipid rafts with methyl-β cyclodextrin enhances actin stress fiber formation and inhibits focal adhesion disassembly, accompanied with alterations in cell morphology. Furthermore, actin cytoskeleton, rather than microtubules, mediates the lipid raft-dependent focal adhesion disassembly by regulating the dephosphorylation of focal adhesion proteins and the internalization of β3 integrin. We also show that Src-RhoA-Rho kinase signaling pathway is responsible for lipid raft disruption-induced stress fiber formation. Taken together, these observations provide a new mechanism to further explain how lipid rafts regulate the migration of melanoma cell and suggest that lipid rafts may be novel and attractive targets for cancer therapy.
Keywords: 4-Morpholineethanesulfonic acid; Actin cytoskeleton; CD; F-actin; Focal adhesion; Lipid raft; MES; Melanoma cell migration; MβCD; PAK-PBD; ROCK; Rho binding domain of Rhotekin; Rho kinase; Rhotekin-RBD; Tyrp; cytochalasin D; filamentous actin; methyl-β cyclodextrin; p21 binding domain of p21-activated kinase 1; tyrosine phosphorylation.
© 2013.