N-乙酰氨基葡萄糖转移酶Ⅴ在肿瘤转移中的作用及其分子机理

Role and Mechanism of N-Acetylglucosaminyltransferases Ⅴ in Tumor Metastasis

目前研究表明N-乙酰氨基葡萄糖转移酶Ⅴ在肿瘤转移中有重要作用.在恶性肿瘤中,N-乙酰氨基葡萄糖转移酶Ⅴ活性增高,其催化产物β1,6分支也增加,β1,6分支与肿瘤的侵袭转移密切相关.本文综述了N-乙酰氨基葡萄糖转移酶Ⅴ催化形成N-糖链β1,6分支的特点以及在N-糖链生物合成中的重要作用;还介绍了N-乙酰氨基葡萄糖转移酶Ⅴ基因组成和参与其基因调控的转录因子Ets-1,及基因表达组织特异性;着重综述了近年来N-乙酰氨基葡萄糖转移酶Ⅴ与肿瘤侵袭转移相关的分子机理的最新研究进展,包括了粘附分子钙粘蛋白(cadherin)和整合素α5β1的作用,修饰表皮生长因子受体调节信号转导,及通过对上皮衍生的细胞表面丝氨酸蛋白酶matriptase的β1,6分支修饰促进仲瘤的侵袭等方面.提示有效抑制N-乙酰氨基葡萄糖转移酶Ⅴ参与作用的位点,为设计抗肿瘤新药提供潜在的治疗靶点.

N-Acetylglucosaminyhransferases Ⅴ（GnT-Ⅴ） plays a pivotal role in cancer progression and metastasis. In tumor, higher activity of GnT-Ⅴ was observed, and the product of GnT-Ⅴ , β1, 6 GlcNAc branching was also increased. And β1, 6 GlcNAc branching is a key structure associated with cancer metastasis. In this review, we demonstrated the research of GnT-Ⅴ , including GnT- Ⅴ catalyzes the formation of β1,6 GlcNac branches of N-glycans and plays a pivotal role in the processing of N-linked glycoproteins, also including structure and expression tissue specific of the GriT- Ⅴ gene, and regulation of GnT- Ⅴ is mediated by a transcription factor Ets-1. The most important part of the review is recently progress of molecular mechanism of GnT-Ⅴ in malignant transformations and cancer metastasis, including GnT-Ⅴ acts on adhesion molecular cadherin and integrin α5β1 and modification of EGF receptor and modify downstream signal transduction, and matriptase with β1,6 GlcNAc branching could increase invasion. Therefore, inhibiting the action of GnT-Ⅴ in terms of the above functions represents a reasonable strategy of new drug design for inhibiting tumor progression and metastasis.