Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1833, Issue 12, Pages 3195-3205Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2013.09.007
Keywords
Lipid raft; Focal adhesion; Actin cytoskeleton; Melanoma cell migration
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Funding
- National Nature Science Foundation of China [81172014, 81071726, 31271509]
- Specialized Research Fund for the Doctoral Program of Higher Education [20100043110007]
- Fundamental Research Funds for the Central Universities [10SSXT129]
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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-p 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 133 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. (C) 2013 Elsevier B.V. All rights reserved.
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