WNT and FGF signaling pathways cross-talk during a variety of cellular 
processes, such as human colorectal carcinogenesis, mouse mammary tumor virus 
(MMTV)-induced carcinogenesis, E2A-Pbx-induced leukemogenesis, early 
embryogenesis, body-axis formation, limb-bud formation, and neurogenesis. 
Canonical WNT signals are transduced through Frizzled receptor and LRP5/6 
coreceptor to downregulate GSK3beta (GSK3B) activity not depending on Ser 9 
phosphorylation. FGF signals are transduced through FGF receptor to the 
FRS2-GRB2-GAB1-PI3K-AKT signaling cascade to downregulate GSK3beta activity 
depending on Ser 9 phosphorylation. Because GSK3beta-dependent phosphorylation 
of beta-catenin and SNAIL leads to FBXW1 (betaTRCP)-mediated ubiquitination and 
degradation, GSK3beta downregulation results in the stabilization and the 
nuclear accumulation of beta-catenin and SNAIL. Nuclear beta-catenin is 
complexed with TCF/LEF, Legless (BCL9 or BCL9L) and PYGO (PYGO1 or PYGO2) to 
activate transcription of CCND1, MYC, FGF18 and FGF20 genes for the cell-fate 
determination. Nuclear SNAIL represses transcription of CDH1 gene, encoding 
E-cadherin, to induce the epithelial-mesenchymal transition (EMT). Mammary 
carcinogenesis in MMTV-Wnt1 transgenic mice is accelerated by MMTV infection due 
to MMTV integration around Fgf3-Fgf4 or Fgf8 loci, and mammary carcinogenesis in 
MMTV-Fgf3 transgenic mice due to MMTV integration around Wnt1-Wnt10b locus. 
Coactivation of WNT and FGF signaling pathways in tumors leads to more malignant 
phenotypes. Single nucleotide polymorphism (SNP) and copy number polymorphism 
(CNP) of WNT and FGF signaling molecules could be utilized as screening method 
of cancer predisposition. cDNA-PCR, microarray or ELISA reflecting aberrant 
activation of WNT and FGF signaling pathways could be developed as novel 
cancer-related biomarkers for diagnosis, prognosis, and therapy. Cocktail 
therapy using WNT and FGF inhibitors, such as small-molecule compounds and human 
neutralizing antibodies, should be developed to increase the efficacy of 
chemotherapy through the inhibition of recurrence by destructing cancer stem 
cells.