Nucleoside Diphosphate Kinase A/nm23-H1 Promotes Metastasis of NB69-Derived Human Neuroblastoma

Author:

Almgren Malin A.E.12,Henriksson K. Cecilia E.12,Fujimoto Jennifer3,Chang Christina L.12

Affiliation:

1. 1Department of Medicine,

2. 2Rebecca and John Moores Cancer Center, and

3. 3Animal Care Program, University of California at San Diego, La Jolla, California

Abstract

Abstract Nucleoside diphosphate kinase A (NDPK-A), encoded by the nm23-H1 gene, acts as a metastasis suppressor in certain human tumors such as breast carcinoma. However, evidence also points to NDPK-A functioning as a metastasis promoter in other human tumors including neuroblastoma. In fact, amplification and overexpression of nm23-H1 as well as S120G mutation of NDPK-A (NDPK-AS120G) have been detected in 14% to 30% of patients with advanced stages of neuroblastoma. To test whether NDPK-A promotes neuroblastoma metastasis, we established stable transfectants and an orthotopic xenograft animal model from the human neuroblastoma NB69 cell line. We demonstrate that overexpressed NDPK-A or NDPK-AS120G increased both incidence and colonization of neuroblastoma metastasis in animal lungs without significantly affecting primary tumor development. In vitro, these metastasis-associated NDPK-A aberrations abrogated retinoic acid-induced neuronal differentiation while increasing cloning efficiency, cell survival, and colony formation of NB69 derivatives. Furthermore, NDPK-AS120G reduced cell adhesion and increased cell migration. Compared with its wild-type, NDPK-AS120G appears more effective in promoting neuroblastoma metastasis. Our results provide the first evidence that NDPK-A behaves as a metastasis promoter at least in human neuroblastoma derived from NB69 cells. The findings not only suggest a prognostic value of NDPK-A in neuroblastoma patients but also caution NDPK-A-targeted treatment for patients with different tumor types.

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology,Molecular Biology

Reference47 articles.

1. Gilles AM, Presecan E, Vonica A, et al. Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem 1991;266:8784-9.

2. Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, et al. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 1988;80:200-4.

3. Backer JM, Mendola CE, Kovesdi I, et al. Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene 1993;8:497-502.

4. Hartsough MT, Steeg PS. Nm23/nucleoside diphosphate kinase in human cancers. J Bioenerg Biomembr 2000;32:301-8.

5. Leone A, Seeger RC, Hong CM, et al. Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas. Oncogene 1993;8:855-65.

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Histidine Phosphorylation: Protein Kinases and Phosphatases;International Journal of Molecular Sciences;2024-07-21

2. Diagnostic significance of NM23 protein in ameloblastoma and ameloblastic carcinoma: An immunohistochemical study;Journal of Stomatology, Oral and Maxillofacial Surgery;2023-12

3. Mechanisms of action of NME metastasis suppressors – a family affair;Cancer and Metastasis Reviews;2023-06-24

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3