WNT antagonist, SFRP1, is Hedgehog signaling target

  • Authors: Yuriko Katoh, Masaru Katoh
  • View Affiliations

  • Published online on: Sunday, January 1, 2006
  • Pages: 171-175
  • DOI: 10.3892/ijmm.17.1.171

Abstract

Hedgehog and WNT signaling pathways network together during embryogenesis and carcinogenesis. Hedgehog signaling in intestinal epithelium represses canonical WNT signaling to restrict expression of WNT target genes to stem or progenitor cells; however, the mechanism remains unclear. The Hedgehog signal is transduced to GLI family transcription factors though Patched receptor, Smoothened signal transducer, and other signaling components, such as KIF27, KIF7, STK36, SUFU, and DZIP1. Here, we searched for the GLI-binding site within the promoter region of genes encoding secreted-type WNT signal inhibitors, including SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, DKK1, DKK2, DKK3, DKK4, and WIF1. The GLI-binding site was identified within the human SFRP1 promoter based on bioinformatics and human intelligence. The chimpanzee SFRP1 gene was identified within the NW_110515.1 genome sequence. The GLI-binding site of the human SFRP1 promoter was conserved in chimpanzee SFRP1, mouse Sfrp1, and rat Sfrp1 promoters. SFRP1 is the evolutionarily conserved target of the Hedgehog-GLI signaling pathway. Expression domain analyses based on text mining revealed that Indian Hedgehog (IHH), SFRP1, and WNT6 are expressed in differentiated intestinal epithelial cells, mesenchymal cells, and stem/progenitor cells, respectively. Hedgehog is secreted from differentiated epithelial cells to induce SFRP1 expression in mesenchymal cells, which keeps differentiated epithelial cells away from the effects of canonical WNT signaling. These facts indicate that SFRP1 is the Hedgehog target to confine canonical WNT signaling within stem or progenitor cells. Therefore, epigenetic CpG hypermethylation of the SFRP1 promoter during chronic persistent inflammation and aging leads to the occurrence of gastrointestinal cancers, such as colorectal cancer and gastric cancer, through the breakdown of Hedgehog-dependent WNT signal inhibition.
Journal Cover

January 2006
Volume 17 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

2012 Impact Factor: 1.957
Ranked #26/121 Medicine Research and Experimental
(total number of cites)

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APA
Katoh, Y., & Katoh, M. (2006). WNT antagonist, SFRP1, is Hedgehog signaling target. International Journal of Molecular Medicine, 17(1), 171-175.
MLA
Katoh, and Masaru Katoh. "WNT antagonist, SFRP1, is Hedgehog signaling target." International Journal of Molecular Medicine International Journal of Molecular Medicine 17.1 (2006): 171-175.
Chicago
Katoh, and Masaru Katoh. "WNT antagonist, SFRP1, is Hedgehog signaling target." International Journal of Molecular Medicine International Journal of Molecular Medicine 17 no. 1 (2006): 171-175.