Cancer Research Center, Xiamen University Medical College, Xiamen 361005, China.
Mol Cancer. 2010 Sep 9;9:236. doi: 10.1186/1476-4598-9-236.
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.
Wnt 和 EGFR 信号通路在胚胎发育和细胞增殖中发挥着关键作用。有大量文献记载，这两条通路的失调常常导致预后不良的肿瘤发生。然而，这两条通路在癌症发展过程中的可能相互作用在很大程度上尚不清楚。虽然有一些报道表明，在果蝇的发育过程中，EGFR 可能拮抗 Wnt 信号通路，但越来越多的证据表明，Wnt 和 EGFR 信号通路在发育和癌症中相互作用并相互激活。本文总结了近年来关于癌症中 Wnt 和 EGFR 信号通路相互作用的研究，并指出了几个可能的汇聚点。Wnt 配体可以通过其 7 次跨膜结构域受体 Frizzled 激活 EGFR 信号通路，而 EGFR 可以通过受体酪氨酸激酶-PI3K/Akt 途径激活 β-catenin；已经表明 EGFR 可以与 β-catenin 形成复合物，增加癌细胞的侵袭和转移。通过与 Dishevelled 相互作用的 Wnt 拮抗剂 NKD2，也可以将含有 TGFα 的胞吐小泡引导到极化上皮细胞的基底外侧膜。NKD2 的下调导致 Wnt 的激活和 TGFα 的错误传递，提示其在细胞稳态和预防肿瘤发生中的功能。
