The Nm23-H1 Metastasis Suppressor as a Translational Target

Eur J Cancer. 2010 May;46(7):1278-82. doi: 10.1016/j.ejca.2010.02.042. Epub 2010 Mar 19.

Abstract

Nm23 was the first of what has become a field of over 20 known metastasis suppressor genes (MSGs). Since the discovery of Nm23 in 1988, a variety of mechanisms have been attributed to its activity, including a histidine kinase activity, binding of other proteins to regulate metastatic formation, and altered gene expression downstream of Nm23. Here, we will review current efforts to translate the previous work done on this MSG into the clinic, including high-dose medroxyprogesterone acetate (MPA), which has been shown to upregulate Nm23 expression. In addition, we will detail a new potential target downstream of Nm23. LPA1 is one of a group of known cell surface receptors for lysophosphatidic acid (LPA), which has been shown to be inversely correlated with Nm23 expression. A specific LPA1 antagonist could conceivably mimic the effects of Nm23 by downregulating the activity of the LPA1 pathway, which would be of considerable interest for potential clinical use.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Genetic Therapy / methods
  • Humans
  • Lysophospholipids / metabolism
  • Lysophospholipids / physiology
  • Medroxyprogesterone Acetate / metabolism
  • Mice
  • NM23 Nucleoside Diphosphate Kinases / genetics
  • NM23 Nucleoside Diphosphate Kinases / physiology*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / therapy*
  • Translational Medical Research / methods

Substances

  • Antineoplastic Agents
  • Lysophospholipids
  • NM23 Nucleoside Diphosphate Kinases
  • Medroxyprogesterone Acetate
  • NME1 protein, human
  • lysophosphatidic acid