7月4日,，《致癌基因》（Oncogene）雜志在線發(fā)表了中科院生物物理研究所閻錫蘊(yùn)研究組的最新研究成果，該文章題為“Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration”,，報(bào)道了細(xì)胞粘附分子CD146促進(jìn)腫瘤細(xì)胞運(yùn)動的分子機(jī)制,。
閻錫蘊(yùn)研究組經(jīng)研究發(fā)現(xiàn)，CD146通過直接結(jié)合ezrin–radixin–moesin (ERM)接頭蛋白與細(xì)胞骨架相連來促進(jìn)細(xì)胞偽足的伸長和細(xì)胞運(yùn)動,。有趣的是,，CD146-ERM復(fù)合物可以結(jié)合小G蛋白的抑制分子Rho-GDI從而激活RhoA，而Rho-PI4P5K通路的激活又進(jìn)一步增強(qiáng)了CD146與ERM的結(jié)合參與腫瘤細(xì)胞的遷移,。
這項(xiàng)研究成果為臨床上過度表達(dá)CD146的黑色素瘤高轉(zhuǎn)移性提供了新的分子機(jī)制,，也為靶向CD146治療腫瘤提供了新的理論基礎(chǔ)。(生物谷 Bioon.com)
生物谷推薦原文出處：
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.
