WW domain-containing oxidoreductase: a candidate tumor suppressor

被引:109
作者
Chang, Nan-Shan [1 ]
Hsu, Li-Jin
Lin, Yee-Shin
Lai, Feng-Jie
Sheu, Hamm-Ming
机构
[1] Natl Cheng Kung Univ, Coll Med, Inst Mol Med, Tainan 70101, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan
[3] Natl Cheng Kung Univ, Coll Med, Ctr Gene Regulat & Signal Transduct Res, Tainan 70101, Taiwan
[4] Natl Cheng Kung Univ, Coll Med, Dept Dermatol, Tainan 70101, Taiwan
[5] Guthrie Res Inst, Sayre, PA 18840 USA
关键词
D O I
10.1016/j.molmed.2006.11.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Common fragile site gene WWOX encodes a candidate tumor suppressor WW domain-containing oxidoreductase. Alteration of this gene, along with dramatic down-regulation 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.
引用
收藏
页码:12 / 22
页数:11
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