Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT - beta-catenin - TCF signaling pathway.
WNT signaling pathway is implicated in embryogenesis as well as in carcinogenesis. We have previously cloned and characterized Frizzled-1 (FZD1), FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, and FZD10, encoding seven-transmembrane-type WNT receptors. Here, expression of FZD10 mRNA in various types of human cancer and effects of FZD10 mRNA microinjection into Xenopus early embryos were investigated. Northern blot analyses revealed relatively high-level expression of 4.0-kb FZD10 mRNA in cervical cancer cell lines HeLa S3, SKG-I, SKG-IIIa, and in a glioblastoma cell line A-172. Matched tumor/normal expression array analysis revealed significant up-regulation of FZD10 mRNA in 2 cases of primary colon cancer. Function of FZD10 was next investigated by using Xenopus axis duplication assay, in which positive regulators of the WNT - beta-catenin - TCF signaling pathway induce axis duplication. Injection of wild-type FZD10 mRNA into the ventral marginal zone of 4-cell-stage Xenopus embryos induced partial axis duplication in 40% of embryos. Ventral injection of Thr579Ala FZD10 mRNA or Val581Leu FZD10 mRNA with mutations in the C-terminal Ser/Thr-X-Val motif also induced partial axis duplication in about 40% of embryos. Furthermore, ventral injection of FZD10 mRNA significantly augmented the potential of co-injected Xenopus wnt-8 (Xwnt-8) mRNA to induce complete axis duplication. These results suggest that up-regulation of FZD10 mRNA in several types of human cells might lead to carcinogenesis through activation of the beta-catenin - TCF signaling pathway synergistically with some class of WNTs.
Terasaki
Harumi
H
Laboratory of Molecular Embryology, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
Saitoh
Tetsuroh
T
Shiokawa
Koichiro
K
Katoh
Masaru
M
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D051157:Frizzled Receptors; D015972:Gene Expression Regulation, Neoplastic; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051153:Wnt Proteins; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000235:genetics; D029961:Zebrafish Proteins; D051176:beta Catenin
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C121168:FZD10 protein, human; D051157:Frizzled Receptors; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C495248:wnt8a protein, Xenopus