Inhibition of signal transduction by the nm23 metastasis suppressor: possible mechanisms.
The first metastasis suppressor gene identified was nm23. Transfection of nm23 into metastatic cell lines resulted in the inhibition of metastasis, but not primary tumor size in vivo. 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. Candidate biochemical mechanisms are identified and discussed herein.
Salerno
Massimiliano
M
Women's Cancers Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. maxsal@mail.nih.gov
Ouatas
Taoufik
T
Palmieri
Diane
D
Steeg
Patricia S
PS
D000818:Animals; D002454:Cell Differentiation; D016147:Genes, Tumor Suppressor; D000071677:Histidine Kinase; D006801:Humans; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D011494:Protein Kinases; D000071677:Histidine Kinase; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins