WW domain-containing oxidoreductase: a candidate tumor suppressor.
Common fragile site gene WWOX encodes a candidate tumor suppressor WW domain-containing oxidoreductase. Alteration of this gene, along with dramatic downregulation of WWOX protein, is shown in the majority of invasive cancer cells. Ectopic WWOX exhibits proapoptotic and tumor inhibitory functions in vitro and in vivo, probably interacting with growth regulatory proteins p53, p73 and others. Hyaluronidases regulate WWOX expression, increase cancer invasiveness and seem to be involved in the development of hormone-independent growth of invasive cancer cells. Estrogen and androgen stimulate phosphorylation and nuclear translocation of WWOX, although binding of WWOX to these sex hormones is unknown. We propose that suppression of WWOX expression by overexpressed hyaluronidases might contribute in part to the development of hormone independence in invasive cancer.
Chang
Nan-Shan
NS
Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan 70101, Republic of China. nschang13827@gmail.com
Hsu
Li-Jin
LJ
Lin
Yee-Shin
YS
Lai
Feng-Jie
FJ
Sheu
Hamm-Ming
HM
D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D040461:Gene Components; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000074584:WW Domain-Containing Oxidoreductase
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D006821:Hyaluronoglucosaminidase