7月4日，《致癌基因》（Oncogene）杂志在线发表了中科院生物物理研究所阎锡蕴研究组的最新研究成果，该文章题为“Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration”，报道了细胞粘附分子CD146促进肿瘤细胞运动的分子机制。

阎锡蕴研究组经研究发现，CD146通过直接结合ezrin–radixin–moesin (ERM)接头蛋白与细胞骨架相连来促进细胞伪足的伸长和细胞运动。有趣的是，CD146-ERM复合物可以结合小G蛋白的抑制分子Rho-GDI从而激活RhoA，而Rho-PI4P5K通路的激活又进一步增强了CD146与ERM的结合参与肿瘤细胞的迁移。

这项研究成果为临床上过度表达CD146的黑色素瘤高转移性提供了新的分子机制，也为靶向CD146治疗肿瘤提供了新的理论基础。

推荐原文出处：

Oncogene   doi:10.1038/onc.2011.244

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

Y Luo, C Zheng, J Zhang, D Lu, J Zhuang, S Xing, J Feng, D Yang, X Yan

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.

购买进口仪器、试剂和耗材——就在始于2001年的毕特博生物 www.bitebo.com