1、Wnt信号通路Wnt 是一类分泌型糖蛋白，通过自分泌或旁分泌发挥作用。在小鼠中，肿瘤病毒整合在 Wnt 之后而导致乳腺癌。卷曲蛋白（Frz）作为 Wnt 受体，其胞外 N 端具有富含半胱氨酸的结构域， Frz 作用于胞质内的蓬乱蛋白（Dsh），Dsh 能切断 -catenin 的降解途径，从而使 -catenin 在细胞质中积累，并进入细胞核，与 T 细胞因子（TCF/LEF）相互作用，调节靶基因的表达。生物学功能多细胞生物体轴分化过程中起重要作用- 连环蛋白调节的典型 Wnt 信号参与前后轴的形成 ；- 连环蛋白敲除的胚胎， 可发生细胞的错误定位，从而不能形成中胚层；抑制 Wnt 信号是脊椎
2、动物体廓形成后期阶段的关键因素；Wnt 拮抗分子能诱导头的形成。 Wnt信号与器官发生Wnt 信号参与大脑的形成。Wnt 3a 敲除的小鼠胚胎，大脑海马回发育受损；Lef 纯合子突变可导致小鼠胚胎缺少全部海马回；Wnt/ LEF/TCF 基因协同作用，共同参与大脑海马回的发育。Wnt 信号参与生长锥的重建和多突触球状环 (苔状神经纤维与颗粒细胞相接触时) 的形成。参与轴突形成的起始过程：Wnt 7a 能诱导苔状神经纤维中轴突和生长锥的重建和触素的汇集。Wnt 信号参与脊椎动物的肢体起始和顶端外胚层脊的形成。三种 Wnt 信号分子( Wnt2b、Wnt3a、Wnt8c)是信号转导的关键诱导者；F
3、GF 与 Wnt 信号的信息交流也与内耳的形成有关。 2 Wnt信号与肿瘤发生Wnt 信号参与肿瘤形成得早期证据来源于小鼠乳腺癌中分离得到的、因病毒插入而激活的癌基因 Int1（见概述）。另外，Wnt 通路的激活突变是小肠早期恶性前病变（包括异常隐窝灶和小息肉）的主要遗传改变。The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals into a cell through cell surface receptors. Three Wnt s
4、ignaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three pathways are activated by binding a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dis
5、hevelled protein inside the cell. The canonical Wnt pathway leads to regulation of gene transcription. The noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell. The noncanonical Wnt/calcium pathway regulates calcium inside the cell. Wnt s
6、ignaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans. Wnt signaling was first identified for its role in carci
7、nogenesis, then for its function in embryonic development. The embryonic processes it controls include body axispatterning, cell fate specification, cell proliferation and cell migration. These processes are necessary for proper formation of important tissues including bone, heart and muscle. Its ro
8、le in embryonic development was discovered when genetic mutations in Wnt pathway proteins produced abnormal fruit fly embryos. Wnt signaling also controls tissue regeneration in adult bone marrow, skin and intestine.Later research found that the genes responsible for these abnormalities also influen
9、ced breast cancer development in mice.Figure 1. Wnt doesnt bind to the receptor. Axin, GSK and APC form a “destruction complex,“ and -Cat is destroyed.Figure 2. Wnt binds to (activates) the receptor. Axin is removed from the “destruction complex.“ -Cat moves into the nucleus, binds to a transcription factor on DNA, and activates transcription of a protein. “P“ represents phosphate.Canonical Wnt pathway
