肿瘤中Axin表达减少的机制及其研究进展  

Advances in research on mechanisms of Axin reduction in tumor

作　　者：周明祎[1] 徐洪涛[2] 

机构地区：[1]中国医科大学,2008级七年制沈阳110001 [2]中国医科大学基础医学院病理学教研室,沈阳110001

出　　处：《国际病理科学与临床杂志》2011年第2期124-128,共5页Journal of International Pathology and Clinical Medicine

基　　金：国家自然科学基金(30801135)~~

摘　　要：Wnt信号转导通路是调控机体发育过程中细胞形状、运动、黏附、增殖、分化、癌变的重要途径之一。轴蛋白Axin是一种体轴发育抑制因子,作为构架蛋白在Wnt信号转导途径中起关键作用,它通过不同的机制调节β连环蛋白(β-catenin)的磷酸化和稳定性。Axin通过与结肠腺瘤性息肉病构架蛋白、糖原合酶激酶3β、β-catenin和酪蛋白激酶1α结合形成复合体促进β-catenin的降解,还通过同源二聚化、核质穿梭、自身磷酸化和稳定性的调控来调节β-catenin的稳定性。Axin通过Wnt信号转导途径参与了一系列生物学效应的调控,如体轴发育、细胞死亡、神经元的分化等。作为一个肿瘤抑制因子,Axin在多种肿瘤中表达减少,是Wnt信号通路的负调控因子,其异常变化与肿瘤的发生、发展及预后密切相关。Axin表达减少的原因尚不明确,目前认为可能与基因突变、启动子甲基化、蛋白降解过多以及多种小分子物质调控有关。本文主要介绍Axin在肿瘤中表达下调的机制的研究新进展。The Wnt signaling pathway plays a critical role in cell shape,movement,adhesion,proliferation and differentiation,and tumor genesis and development.Axin is an inhibitor of axis.As a scaffold protein,it plays a key role in the Wnt signaling pathway.Axin regulates the phosphorylation and stability of β-catenin via different mechanisms.It facilitates β-catenin degradation by assembling a β-catenin destruction complex,which includes adenomatous polyposis coli（APC）,glycogen synthase kinase 3β（GSK3β）,β-catenin,casein kinase 1α（CK1α）,and Axin itself.The homodimerization,nuclear cytoplasmic shuttling,phosphorylation and stability of axin also play important roles in β-catenin regulation.Through Wnt signaling pathway,Axin participates in the regulations of serial biological effects such as axis development,cell death,neuronal differentiation,and so on.As a tumor inhibitor,Axin protein expression decreases in many malignant carcinoma.The mechanism of Axin reduction is still unclear.It may be associated with gene mutation,promoter methylation,protein degradation,and various small molecules.This review mainly summarized the latest progress in research on mechanism of Axin reduction.

关 键 词：轴蛋白 酪蛋白激酶1 散乱蛋白 Pyrvinium 

分 类 号：R730.2[医药卫生—肿瘤]