| First Author | Lujambio A | Year | 2013 |
| Journal | Cell | Volume | 153 |
| Issue | 2 | Pages | 449-60 |
| PubMed ID | 23562644 | Mgi Jnum | J:197241 |
| Mgi Id | MGI:5491962 | Doi | 10.1016/j.cell.2013.03.020 |
| Citation | Lujambio A, et al. (2013) Non-cell-autonomous tumor suppression by p53. Cell 153(2):449-60 |
| abstractText | The p53 tumor suppressor can restrict malignant transformation by triggering cell-autonomous programs of cell-cycle arrest or apoptosis. p53 also promotes cellular senescence, a tumor-suppressive program that involves stable cell-cycle arrest and secretion of factors that modify the tissue microenvironment. In the presence of chronic liver damage, we show that ablation of a p53-dependent senescence program in hepatic stellate cells increases liver fibrosis and cirrhosis associated with reduced survival and enhances the transformation of adjacent epithelial cells into hepatocellular carcinoma. p53-expressing senescent stellate cells release factors that skew macrophage polarization toward a tumor-inhibiting M1-state capable of attacking senescent cells in culture, whereas proliferating p53-deficient stellate cells secrete factors that stimulate polarization of macrophages into a tumor-promoting M2-state and enhance the proliferation of premalignant cells. Hence, p53 can act non-cell autonomously to suppress tumorigenesis by promoting an antitumor microenvironment, in part, through secreted factors that modulate macrophage function. |
