Tumor suppressor p53 and its homologue p73alpha affect cell migration.
The p53 tumor suppressor plays a central role in the negative control of growth and survival of abnormal cells. Previously we demonstrated that in addition to these functions, p53 expression affects cell morphology and lamellar activity of the cell edge (Alexandrova, A., Ivanov, A., Chumakov, P. M., Kopnin, P. B., and Vasiliev, J. M. (2000) Oncogene 19, 5826-5830). In the present work we studied the effects of p53 and its homologue p73alpha on cell migration. We found that loss of p53 function correlated with decreased cell migration that was analyzed by in vitro wound closure test and Boyden chamber assay. The decreased motility of p53-deficient cells was observed in different cell contexts: human foreskin fibroblasts (BJ), human colon and lung carcinoma cell lines (HCT116 and H1299, respectively), as well as mouse normal fibroblasts from lung and spleen, peritoneal macrophages, and keratinocytes. On the other hand, overexpression of the p53 family member p73alpha stimulated cell migration. Changes in cell migration correlated directly with transcription activation induced by p53 or p73alpha. Noteworthy, p53 modulated cell motility in the absence of stress. The effect of p53 and p73alpha on cell migration was mediated through the activity of the phosphatidylinositol 3-kinase/Rac1 pathway. This p53/p73 function was mainly associated with some modulation of intracellular signaling rather than with stimulation of production of secreted motogenic factors. The identified novel activity of the p53 family members might be involved in regulation of embryogenesis, wound healing, or inflammatory response.
Lerner Research Institute, the Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Anna A
AA
Sablina
Peter M
PM
Chumakov
Boris P
BP
Kopnin
D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology*; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D049452:Green Fluorescent Proteins; D006801:Humans; D007249:Inflammation; D007797:Laminin / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation; D014945:Wound Healing
D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007797:Laminin; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D011509:Proteoglycans; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen