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

  • Ram Krishna Thakur
  • Vinod Kumar Yadav
  • Pankaj Kumar
  • Shantanu Chowdhury


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.


NM23 Meta-analysis Metastasis Transcription Metastasis suppression Regulation NME2 promoter NM23 H2 



We thank all members of SC lab for helpful discussion. Research grant from CSIR (MLP 5501), DST (Swarnajayanti Fellowship to SC), and Senior Research Fellowship to VKY (CSIR) and PK (ICMR) is acknowledged. Gene expression datasets from multiple tumor types for analysis of NME2 transcript level were obtained from expO (IGC, USA, Datasets for ChIP-seq analysis were from ENCODE consortium (

Conflicts of interest



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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ram Krishna Thakur
    • 1
  • Vinod Kumar Yadav
    • 2
  • Pankaj Kumar
    • 2
  • Shantanu Chowdhury
    • 1
    • 2
  1. 1.Proteomics and Structural Biology UnitInstitute of Genomics and Integrative Biology, CSIRDelhiIndia
  2. 2.G.N.R. Knowledge Centre for Genome InformaticsInstitute of Genomics and Integrative Biology, CSIRDelhiIndia

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