Convergence between Wnt-β-catenin and EGFR signaling in cancer.
Convergence between Wnt-β-catenin and EGFR signaling in cancer.
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DOI：
10.1186/1476-4598-9-236
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发表时间：
2010-09-09
期刊：
影响因子：
37.3
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Hu T;Li C
WNT和EGFR信号在胚胎发育和细胞增殖中起关键作用。已有文献表明，这两条通路的失调往往会导致肿瘤的发生，并导致预后不良。然而，这两条途径在癌症发展过程中可能存在的串扰在很大程度上是未知的。虽然有报道表明，在果蝇发育过程中，EGFR可能会拮抗Wnt信号，但越来越多的证据表明，在发育和癌症过程中，Wnt和EGFR信号相互串扰和反式激活。本文综述了近年来关于肿瘤中Wnt和EGFR信号之间的串扰的研究，并指出了几个可能的趋同点。WNT配体通过其7-跨膜区受体Frizzled型激活表皮生长因子受体信号，而表皮生长因子受体通过受体酪氨酸激酶-PI3K/AKT途径激活β-连环蛋白，与β-连环蛋白形成复合体，增加癌细胞的侵袭和转移。NKD2是一种Wnt拮抗剂，通过与杂乱的细胞相互作用，也将含有转化生长因子α的胞外囊泡护送到极化上皮细胞的基侧膜上。NKD2的下调导致Wnt激活和转化生长因子α的错误传递，提示其在细胞动态平衡和预防肿瘤发生中的作用。
Wnt and EGFR signaling play key roles in embryonic development and cell proliferation. It is well documented that dysregulation of these two pathways often leads to tumorigenesis with poor prognosis. However, the possible crosstalk between the two pathways in cancer development is largely unknown. Although some reports show that EGFR might antagonize Wnt signaling during development in Drosophila, an increasing body of evidence indicates that Wnt and EGFR signaling crosstalk and transactivate one another in development and cancer. This review summarizes recent studies on the crosstalk between Wnt and EGFR signaling in cancers and points out several possible convergence points. Wnt ligands can activate EGFR signaling through their 7-transmembrane domain receptor Frizzled while EGFR can activate β-catenin via receptor tyrosine kinase-PI3K/Akt pathway; EGFR has been shown to form a complex with β-catenin and increase the invasion and metastasis of cancer cells. NKD2, a Wnt antagonist by interacting with Dishevelled, also escorts TGFα-containing exocytic vesicles to the basolateral membrane of polarized epithelial cells. Down-regulation of NKD2 causes Wnt activation and TGFα misdelivery, suggesting its functions in cell homeostasis and prevention of tumorigenesis.
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