Expression of the FAT10 gene is highly upregulated in hepatocellular carcinoma and other gastrointestinal and gynecological cancers.
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.
Department of Biochemistry, National University of Singapore, Singapore. bchleec@nus.edu.sg
Caroline G L
CG
Lee
Jianwei
J
Ren
Ian S Y
IS
Cheong
Kenneth H K
KH
Ban
London L P J
LL
Ooi
Soo
S
Yong Tan
Alison
A
Kan
Issarang
I
Nuchprayoon
Rongxian
R
Jin
Kang-Hoe
KH
Lee
Michael
M
Choti
Linda A
LA
Lee
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism; D005833:Genital Neoplasms, Female / Q000378:metabolism; D006801:Humans; D009928:Organ Specificity; D014407:Tumor Cells, Cultured; D014452:Ubiquitins; D015854:Up-Regulation
D002352:Carrier Proteins; C109184:UBD protein, human; D014452:Ubiquitins