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PMID: 21556888 Published · ppublish English Journal Article Meta-Analysis Research Support, Non-U.S. Gov't

Mechanisms of non-metastatic 2 (NME2)-mediated control of metastasis across tumor types.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 384 ·No. 4-5 ·2011-10-00 ·Pages 397-406

Thakur RK, Yadav VK, Kumar P, Chowdhury S

Abstract

Non-metastatic 23 [NM23/nucleoside diphosphate kinases (NDPK)] genes are the first discovered metastasis suppressor genes. More than two decades of research has demonstrated their roles in a variety of biological processes with NME1 and NME2 being most studied in the context of metastasis suppression. Although NME1 and NME2 share >85% homology at amino acid level, they show redundant as well as unique molecular functions. Phenotypic analyses of knockout (KO) mice for NM23 members (NDPK-A, B) and compound KO (A as well as B) showed requirement of both proteins in hematopoiesis suggesting shared functions in development disease. Several reviews have discussed NME1, however the role of NME2 appears to be relatively less understood in the context of metastasis suppression. Here, we focus on NME2 and by meta-analysis of gene expression from multiple tumor types, and survey of in vivo and vitro studies, suggest the possibility that NME2 may be one of the key factors in metastasis. This along with the relevance of normal physiological functions of NME2 in the context of metastasis is discussed. We further examined the genetic and epigenetic features of NME2 and NME1 gene promoters and found aspects of transcription control that could be unique to NME2/NME1. Findings on signaling pathways and small molecules which regulate the expression of NME2 that could be therapeutically important are also discussed.

MeSH Terms
Animals Binding Sites Cell Line, Tumor Gene Expression Humans NM23 Nucleoside Diphosphate Kinases/genetics,physiology Neoplasm Metastasis Neoplasms/enzymology,genetics,pathology Transcription Factors/metabolism
Chemicals
NM23 Nucleoside Diphosphate Kinases Transcription Factors NME2 protein, human Nme2 protein, mouse
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Thakur Ram Krishna
Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110 007, India.
Yadav Vinod Kumar
Kumar Pankaj
Chowdhury Shantanu
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Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
1432-1912
DOI
10.1007/s00210-011-0631-0
Published
2011-10-00
Epub
2011-00-10
Pages
397-406
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/s00210-011-0631-0 View journal details
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