Contrasting activity of Hedgehog and Wnt pathways according to gastric cancer cell differentiation: Relevance of crosstalk mechanisms

Jie Hyun Kim, Hyun Soo Shin, Sang Hun Lee, Inohk Lee, Yeo Song Lee, Jun Chul Park, Yu Jin Kim, Jae Bock Chung, Yong Chan Lee

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Gastric cancer displays different biological behaviors according to histological differentiation. The different biological behavior might involve the activation of distinct signaling pathways necessary for the growth and survival of cancer cells in gastric cancer. We investigated the differentiation-related signal interaction between Hedgehog and Wnt pathways in gastric cancer cells. Differentiation of gastric cancer cells was induced by sodium butyrate. The sonic Hedgehog (SHH) signal expressions were increased during cellular differentiation. In contrast, the expression of Wnt signaling was decreased during differentiation. Ectopic expression of glioma-associated oncogene-1 (GLI1) increased the level of secreted frizzled related protein-1 (SFRP1) transcript, whereas inhibition of GLI1 reduced the level of SFRP1 transcript. ChIP assay showed that GLI1 induced the transcriptional regulation of SFRP1 gene expression. Ectopic expression of GLI1 decreased the nuclear β-catenin staining, but the inhibition of GLI1 induced the reversal of nuclear β-catenin overexpression. Ectopic expression of β-catenin also decreased the expression of GLI1 in the butyrate treated cancer cells. SHH and GLI1 immunoexpression was greater in well differentiated gastric cancer tissues compared to poorly differentiated tissues, and nuclear β-catenin immunoexpression was lower in well differentiated compared to poorly differentiated tissues. The SHH and Wnt pathways are differentially involved according to gastric cancer cell differentiation.

Original languageEnglish
Pages (from-to)328-335
Number of pages8
JournalCancer Science
Volume101
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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