SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway

Yu Lueng Shih, Chung B. Hsieh, Hung Cheng Lai, Ming D. Yan, Tsai Yuan Hsieh, You Chen Chao, Ya W. Lin

研究成果: 雜誌貢獻文章

69 引文 (Scopus)

摘要

Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications for carcinogenesis. Promoter hypermethylation of SFRP genes is common in human cancers. However, the role of SFRPs in HCC is not clear. Recently, we have shown that SFRP1 is frequently downregulated through promoter hypermethylation. To confirm and extend these findings, the methylation status of the other SFRP members, including SFRP2, SFRP4 and SFRP5, was examined by methylation-specific polymerase chain reaction (MS-PCR). Hypermethylation of SFRP genes, except for SFRP4, is frequent in HCCs and the levels found here were significantly higher than those seen in cirrhotic livers, chronic hepatitis livers and normal controls (p <0.0001 for SFRP1 and SFRP2, p <0.05 for SFRP5). To investigate the role of SFRP1 in HCCs, we used re-expression of SFRP1 in β-catenin-dependent HCC cell lines: Huh6 and HepG2. Restoration of SFRP1 attenuated Wnt signaling in those Huh6 hepatoma cells with a β-catenin gene point mutation, decreased abnormal accumulation of p-catenin in the nucleus and suppressed cell growth. Conversely, restoration of SFRP1 in HepG2 hepatoma cells with truncated β-catenin could not block the Wnt signaling pathway. Furthermore, knocking down SFRP1 by RNA interference in β-catenin-deficient cell lines (SK-Hep1) stimulated Wnt signaling and promoted cell growth. Our data suggested that SFRP1 suppressed liver cancer cells growth through Wnt canonical signaling. Moreover, β-catenin- independent noncanonical pathway might be involved in Wnt signaling activation through unknown molecules in HCC.

原文英語
頁(從 - 到)1028-1035
頁數8
期刊International Journal of Cancer
121
發行號5
DOIs
出版狀態已發佈 - 九月 1 2007
對外發佈Yes

指紋

Catenins
Wnt Signaling Pathway
Hepatocellular Carcinoma
Growth
Methylation
Genes
Cell Line
Liver
Hep G2 Cells
Chronic Hepatitis
Liver Neoplasms
RNA Interference
Cell Nucleus
Point Mutation
Carcinogenesis
Down-Regulation
FRZB protein
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

Shih, Y. L., Hsieh, C. B., Lai, H. C., Yan, M. D., Hsieh, T. Y., Chao, Y. C., & Lin, Y. W. (2007). SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway. International Journal of Cancer, 121(5), 1028-1035. https://doi.org/10.1002/ijc.22750

SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway. / Shih, Yu Lueng; Hsieh, Chung B.; Lai, Hung Cheng; Yan, Ming D.; Hsieh, Tsai Yuan; Chao, You Chen; Lin, Ya W.

於: International Journal of Cancer, 卷 121, 編號 5, 01.09.2007, p. 1028-1035.

研究成果: 雜誌貢獻文章

Shih, YL, Hsieh, CB, Lai, HC, Yan, MD, Hsieh, TY, Chao, YC & Lin, YW 2007, 'SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway', International Journal of Cancer, 卷 121, 編號 5, 頁 1028-1035. https://doi.org/10.1002/ijc.22750
Shih, Yu Lueng ; Hsieh, Chung B. ; Lai, Hung Cheng ; Yan, Ming D. ; Hsieh, Tsai Yuan ; Chao, You Chen ; Lin, Ya W. / SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway. 於: International Journal of Cancer. 2007 ; 卷 121, 編號 5. 頁 1028-1035.
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abstract = "Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications for carcinogenesis. Promoter hypermethylation of SFRP genes is common in human cancers. However, the role of SFRPs in HCC is not clear. Recently, we have shown that SFRP1 is frequently downregulated through promoter hypermethylation. To confirm and extend these findings, the methylation status of the other SFRP members, including SFRP2, SFRP4 and SFRP5, was examined by methylation-specific polymerase chain reaction (MS-PCR). Hypermethylation of SFRP genes, except for SFRP4, is frequent in HCCs and the levels found here were significantly higher than those seen in cirrhotic livers, chronic hepatitis livers and normal controls (p <0.0001 for SFRP1 and SFRP2, p <0.05 for SFRP5). To investigate the role of SFRP1 in HCCs, we used re-expression of SFRP1 in β-catenin-dependent HCC cell lines: Huh6 and HepG2. Restoration of SFRP1 attenuated Wnt signaling in those Huh6 hepatoma cells with a β-catenin gene point mutation, decreased abnormal accumulation of p-catenin in the nucleus and suppressed cell growth. Conversely, restoration of SFRP1 in HepG2 hepatoma cells with truncated β-catenin could not block the Wnt signaling pathway. Furthermore, knocking down SFRP1 by RNA interference in β-catenin-deficient cell lines (SK-Hep1) stimulated Wnt signaling and promoted cell growth. Our data suggested that SFRP1 suppressed liver cancer cells growth through Wnt canonical signaling. Moreover, β-catenin- independent noncanonical pathway might be involved in Wnt signaling activation through unknown molecules in HCC.",
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AU - Lai, Hung Cheng

AU - Yan, Ming D.

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AU - Chao, You Chen

AU - Lin, Ya W.

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AB - Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications for carcinogenesis. Promoter hypermethylation of SFRP genes is common in human cancers. However, the role of SFRPs in HCC is not clear. Recently, we have shown that SFRP1 is frequently downregulated through promoter hypermethylation. To confirm and extend these findings, the methylation status of the other SFRP members, including SFRP2, SFRP4 and SFRP5, was examined by methylation-specific polymerase chain reaction (MS-PCR). Hypermethylation of SFRP genes, except for SFRP4, is frequent in HCCs and the levels found here were significantly higher than those seen in cirrhotic livers, chronic hepatitis livers and normal controls (p <0.0001 for SFRP1 and SFRP2, p <0.05 for SFRP5). To investigate the role of SFRP1 in HCCs, we used re-expression of SFRP1 in β-catenin-dependent HCC cell lines: Huh6 and HepG2. Restoration of SFRP1 attenuated Wnt signaling in those Huh6 hepatoma cells with a β-catenin gene point mutation, decreased abnormal accumulation of p-catenin in the nucleus and suppressed cell growth. Conversely, restoration of SFRP1 in HepG2 hepatoma cells with truncated β-catenin could not block the Wnt signaling pathway. Furthermore, knocking down SFRP1 by RNA interference in β-catenin-deficient cell lines (SK-Hep1) stimulated Wnt signaling and promoted cell growth. Our data suggested that SFRP1 suppressed liver cancer cells growth through Wnt canonical signaling. Moreover, β-catenin- independent noncanonical pathway might be involved in Wnt signaling activation through unknown molecules in HCC.

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