NM23-H1: a Metastasis-Associated Gene

Tee, Yi-Torng; Chen, Gin-Den; Lin, Long-Yau; Ko, Jiunn-Liang; Wang, Po-Hui

doi:10.1016/S1028-4559(09)60206-0

« Previous Next »Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 2 , Pages 107-113, June 2006

NM23-H1: a Metastasis-Associated Gene

Yi-Torng Tee
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Taichung, Taiwan
Gin-Den Chen
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Taichung, Taiwan
Long-Yau Lin
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Taichung, Taiwan
- School of Medicine, Taichung, Taiwan
Jiunn-Liang Ko
- Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan
Po-Hui Wang
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Taichung, Taiwan
- School of Medicine, Taichung, Taiwan
- Correspondence to: Dr Po-Hui Wang, Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo North Road, Taichung 40201, Taiwan

Accepted 21 March 2006.

Summary

The protein product of nm23-H1 gene has activity of nucleoside diphosphate (NDP) kinase, which catalyzes the phosphorylation of nucleoside diphosphates to the corresponding nucleoside triphosphates. Reductions in nm23 expression have been significantly associated with aggressive behavior in melanoma, breast, colon, and gastric carcinomas. On the contrary, high levels of nm23 gene expression are noted in the advanced stage of thyroid carcinomas and associated with significant reductions in survival for neuroblastoma and osteosarcoma patients. Although expression of nm23/NDP kinase is divergent in various malignant tumors, its reduced expression seems to be related to increased metastatic potential in most carcinoma types. However, it is hypothesized that nm23 may play a tissue-specific role, and that different regulatory mechanisms may act in different tumors. In ovarian carcinoma, nm23-H1/NDP kinase may be correlated with some clinicopathologic characteristics. In cervical cancer, nm23-H1 is probably involved in cervical carcinogenesis and correlated with some aggressive parameters. Overexpression of nm23-H1 protein may indicate poor survival for cervical cancer patients. Other than histidine 118 residue (amino acid sequence 118: histidine) concerned with NDP kinase activity of nm23-H1, serine 120 (amino acid sequence 120: serine) related activity of histidine-dependent protein phosphotransfer was recently reported to be responsible for its biological suppressive effects. To inhibit metastatic potential, nm23-H1 is also demonstrated to co-immunoprecipitate the kinase suppressor of Ras and phosphorylate it, and therefore reduce activation of the extracellular signal-regulated kinase mitogen-activated protein kinase pathway in response to signaling.

Key Words: high-grade squamous intraepithelial lesion , kinase suppressor of Ras , metastasis , Nm23-H1 , nucleoside diphosphate kinase , squamous cell carcinoma