Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. In a recent study reported in the journal Oncogene, Professor YAN Xiyun and colleagues at the National Laboratory of Biomacromolecules, and the Chinese Academy of Sciences—University of Tokyo Joint Laboratory of Structural Virology and Immunology investigated the molecular mechanism by which melanoma cell migration is promoted by CD146, an integral membrane glycoprotein belonging to the immunoglobulin superfamily whose expression correlates with the malignant progression and metastatic potential of human melanoma cells.

They report that CD146 physically interacts with highly-conserved actin-linking ezrin–radixin–moesin (ERM) proteins, proteins which provide a regulatable link between membrane-associated proteins and the cortical cytoskeleton and also participate in signal transduction, leading to local cytoskeleton remodelling. As a result of this interaction, ERM proteins are recruited to cell protrusions, promoting the formation and elongation of microvilli. Professor Yan and colleagues further show that CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) via ERM proteins and thus sequesters RhoGDI1 from RhoA, leading to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through the Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, reinforcing the CD146/ERM association.

These results from Professor Yan’s lab provide a mechanistic basis for understanding the role of CD146 in regulating human melanoma cell motility and suggest therapeutic targets for preventing cancer metastasis.

Oncogene (2012) 31, 306–321; doi:10.1038/onc.2011.244

Pig.  CD146, an ERM-binding protein, is involved in regulating cell migration.