SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation-dependent and -independent mechanisms

  • Authors:
    • Hiroshi Yoshibayashi
    • Hiroshi Okabe
    • Seiji Satoh
    • Koya Hida
    • Kazuhiko Kawashima
    • Shinya Hamasu
    • Akinari Nomura
    • Suguru Hasegawa
    • Iwao Ikai
    • Yoshiharu Sakai
  • View Affiliations

  • Published online on: March 1, 2007     https://doi.org/10.3892/or.17.3.549
  • Pages: 549-556
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Abstract

We have previously shown that expression of SIAH1 is frequently down-regulated in HCCs and associated with their advanced stages. It has been shown that SIAH1 functions in the phosphorylation-independent degradation of β-catenin and induces apoptosis and growth arrest. To examine if the effects of SIAH1 overexpression depend on the altered β-catenin signaling pathway, we transferred the SIAH1 gene into three hepatoma cell lines with different genetic backgrounds: HepG2 (mutant β-catenin), SNU475 (mutant AXIN1), and Huh7 cells (wild type β-catenin and AXIN1). SIAH1 significantly decreased aberrant β-catenin signal in HepG2 and SNU475 cells and induced growth arrest and apoptosis. However, SIAH1 also induced apoptosis in Huh7 cells, which retained a normal membranous distribution pattern of β-catenin. Immunoblotting study demonstrated that SIAH1 also reduces the amount of PEG10 protein, which is known to be frequently overexpressed in HCC and to promote cell proliferation. These data suggest that PEG10 is another target protein of SIAH1 to induce apoptosis in hepatoma cells. Our results should lead to a better understanding of the relationship between deregulation of β-catenin signals and hepatocarcinogenesis. Further investigations into the mechanisms by which SIAH1 promotes apoptosis and suppresses cell growth should also allow for the discovery of new therapeutic strategies.

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March 2007
Volume 17 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yoshibayashi H, Okabe H, Satoh S, Hida K, Kawashima K, Hamasu S, Nomura A, Hasegawa S, Ikai I, Sakai Y, Sakai Y, et al: SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation-dependent and -independent mechanisms. Oncol Rep 17: 549-556, 2007
APA
Yoshibayashi, H., Okabe, H., Satoh, S., Hida, K., Kawashima, K., Hamasu, S. ... Sakai, Y. (2007). SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation-dependent and -independent mechanisms. Oncology Reports, 17, 549-556. https://doi.org/10.3892/or.17.3.549
MLA
Yoshibayashi, H., Okabe, H., Satoh, S., Hida, K., Kawashima, K., Hamasu, S., Nomura, A., Hasegawa, S., Ikai, I., Sakai, Y."SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation-dependent and -independent mechanisms". Oncology Reports 17.3 (2007): 549-556.
Chicago
Yoshibayashi, H., Okabe, H., Satoh, S., Hida, K., Kawashima, K., Hamasu, S., Nomura, A., Hasegawa, S., Ikai, I., Sakai, Y."SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation-dependent and -independent mechanisms". Oncology Reports 17, no. 3 (2007): 549-556. https://doi.org/10.3892/or.17.3.549