Basic and translational advances in cancer metastasis: Nm23.
Cancer metastasis is a significant contributor to breast cancer patient morbidity and mortality. To develop new anti-metastatic therapies, we need to understand the biological and biochemical mechanisms of metastasis. Toward these efforts, we and others have studied metastasis suppressor genes, which halt metastasis in vivo without affecting primary tumor growth. The first metastasis suppressor gene confirmed was nm23, also known as NDP kinase. Using in vitro assays, nm23 overexpression resulted in reduced anchorage-independent colonization in response to TGF-beta, reduced invasion and motility in response to multiple factors, and increased differentiation. We hypothesize that the mechanism of action of Nm23 in metastasis suppression involves diminished signal transduction, downstream of a particular receptor. We hypothesize that a histidine protein kinase activity of Nm23 underlies its suppression of metastasis, and identify candidate substrates. This review also discusses therapeutic options on the basis of reexpression of metastasis suppressors.
Ouatas
Taoufik
T
Women's Cancers Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. taoufik@mail.nih.gov
Salerno
Massimiliano
M
Palmieri
Diane
D
Steeg
Patricia S
PS
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D002278:Carcinoma in Situ / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000235:genetics / Q000556:secondary / Q000628:therapy; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008207:Lymphatic Metastasis; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000628:therapy; D009701:Nucleoside-Diphosphate Kinase; D014176:Protein Biosynthesis / Q000235:genetics*; D011506:Proteins / Q000378:metabolism*
D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase