title: Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration.
abstract: Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility.
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors: Y
authors: Y
authors: Luo
authors: C
authors: C
authors: Zheng
authors: J
authors: J
authors: Zhang
authors: D
authors: D
authors: Lu
authors: J
authors: J
authors: Zhuang
authors: S
authors: S
authors: Xing
authors: J
authors: J
authors: Feng
authors: D
authors: D
authors: Yang
authors: X
authors: X
authors: Yan
mesh_terms: D051929:CD146 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008871:Microvilli / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010766:Phosphorylation; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D051929:CD146 Antigen; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; C497902:MCAM protein, human; D019269:Phosphatidylinositol 4,5-Diphosphate; D014157:Transcription Factors; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; C066737:RHOA protein, human; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein