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Expression of the FAT10 gene is highly upregulated in hepatocellular carcinoma and other gastrointestinal and gynecological cancers

Oncogene volume 22, pages 2592–2603 (2003)Cite this article

Abstract

The ubiquitin-like modifier (UBL) family has recently generated much interest in the scientific community, as it is implicated to play important regulatory roles via novel protein–protein modification. FAT10 (diubiquitin) belongs to this family of proteins, comprising two ubiquitin-like moieties fused in tandem, and has been implicated to be involved in the maintenance of spindle integrity during mitosis. As FAT10 may play a role in the regulation of genomic stability, we examined if there is an association between FAT10 expression and hepatocellular carcinoma (HCC) or other cancers. Northern blot analyses revealed upregulation of FAT10 expression in the tumors of 90% of HCC patients. In situ hybridization as well as immunohistochemistry utilizing anti-FAT10 antibodies localized highest FAT10 expression in the nucleus of HCC hepatocytes rather than the surrounding immune and non-HCC cells. FAT10 expression was also found to be highly upregulated in other cancers of the gastrointestinal tract and female reproductive system. In conclusion, we demonstrated upregulation of FAT10 expression in various gastrointestinal and gynecological cancers. Its overexpression is unrelated to the general increase in protein synthesis or a general immune/inflammatory response to cancer. Rather, FAT10 may modulate tumorigenesis through its reported interaction with the MAD2 spindle-assembly checkpoint protein.

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Acknowledgements

We are greatly indebted to Professor Chi V Dang, Department of Medicine, Johns Hopkins University School of Medicine, USA, for his invaluable guidance and advice throughout this project. We thank Dr Samuel S Chong, Department of Pediatrics and Obstetrics and Gynecology, NUS for the provision of the pCMVDsRed plasmid and critical review of the manuscript. We acknowledge the Thailand Research Fund Grant Number RSA04/2540 (to IN) and the National Cancer Center Tissue Repository in Singapore for providing HCC tissues used in this study. This work was funded by grants from the Agency for Science, Technology and Research of Singapore, through Johns Hopkins Singapore (to CGLL and LAL) as well as SingHealth Cluster Research Fund through the National Cancer Center to CGLL (BF015/2002).

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  1. Contributed equally to this work

Authors and Affiliations

  1. Department of Biochemistry, National University of Singapore, Singapore

    Caroline GL Lee, Ian SY Cheong & Kenneth HK Ban

  2. Division of Medical Sciences, National Cancer Center, Singapore

    Caroline GL Lee, Jianwei Ren, Alison Kan & Rongxian Jin

  3. Johns Hopkins Singapore, Singapore

    Caroline GL Lee, Jianwei Ren, Rongxian Jin & Linda A Lee

  4. Departments of Medicine, Johns Hopkins University School of Medicine, USA

    Caroline GL Lee & Linda A Lee

  5. Department of Surgical Oncology, National Cancer Center, Singapore

    London LPJ Ooi

  6. Department of Surgery, Singapore General Hospital, Singapore

    London LPJ Ooi

  7. Department of Pathology and Laboratory Medicine, Tan Tock Seng Hospital, Singapore

    Soo Yong Tan

  8. Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Thailand

    Issarang Nuchprayoon

  9. Department of Medicine, National University Hospital, Singapore

    Kang-Hoe Lee

  10. Department of Surgery, Johns Hopkins University School of Medicine, USA

    Michael Choti

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  1. Caroline GL Lee
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Correspondence to Caroline GL Lee.

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Lee, C., Ren, J., Cheong, I. et al. Expression of the FAT10 gene is highly upregulated in hepatocellular carcinoma and other gastrointestinal and gynecological cancers. Oncogene 22, 2592–2603 (2003). https://doi.org/10.1038/sj.onc.1206337

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