title: Convergence between Wnt-β-catenin and EGFR signaling in cancer.
abstract: 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.
authors.affiliation: Cancer Research Center, Xiamen University Medical College, Xiamen 361005, China. thu@xmu.edu.cn
authors.forename: Tianhui
authors.initials: T
authors.lastname: Hu
authors.forename: Cunxi
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D066246:ErbB Receptors