Clinical-translational approaches to the Nm23-H1 metastasis Suppressor

Patricia S. Steeg, Christine E. Horak, Kathy Miller

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Nm23-H1 significantly reduces metastasis without effects on primary tumor size and was the first discovered metastasis suppressor gene. At least three mechanisms are thought to contribute to the metastasis-suppressive effect of Nm23-H1: (a) its histidine kinase activity toward ATP-citrate lyase, aldolase C, and the kinase suppressor of ras, with the last inactivating mitogen-activated protein kinase signaling; (b) binding proteins that titer out "free" Nm23-H1 and inhibit its ability to suppress metastasis; and (c) altered gene expression downstream of Nm23-H1, particularly an inverse association with the lysophosphatidic acid receptor endothelial differentiation gene-28 (EDG2). Most metastasis suppressor genes, including Nm23-H1, affect metastatic colonization, which is the outgrowth of tumor cells in distant locations; therefore, they are of high translational interest. A phase II trial is ongoing to test the hypothesis that a compound, high-dose medroxyprogesterone acetate (MPA), used as an unconventional gluocorticoid, will stimulate breast cancer cells to reexpress Nm23-H1 and limit subsequent metastatic colonization.

Original languageEnglish
Pages (from-to)5006-5012
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number16
DOIs
StatePublished - Aug 15 2008

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Neoplasm Metastasis
Tumor Suppressor Genes
ATP Citrate (pro-S)-Lyase
Lysophosphatidic Acid Receptors
Medroxyprogesterone Acetate
Fructose-Bisphosphate Aldolase
Mitogen-Activated Protein Kinases
Neoplasms
Carrier Proteins
Breast Neoplasms
Gene Expression
Genes
Histidine Kinase
KSR-1 protein kinase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Clinical-translational approaches to the Nm23-H1 metastasis Suppressor. / Steeg, Patricia S.; Horak, Christine E.; Miller, Kathy.

In: Clinical Cancer Research, Vol. 14, No. 16, 15.08.2008, p. 5006-5012.

Research output: Contribution to journalArticle

Steeg, Patricia S. ; Horak, Christine E. ; Miller, Kathy. / Clinical-translational approaches to the Nm23-H1 metastasis Suppressor. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 16. pp. 5006-5012.
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