Non-cell-autonomous tumor suppression by p53 Journal Article
| Authors: | Lujambio, A.; Akkari, L.; Simon, J.; Grace, D.; Tschaharganeh, D. F.; Bolden, J. E.; Zhao, Z.; Thapar, V.; Joyce, J. A.; Krizhanovsky, V.; Lowe, S. W. |
| Article Title: | Non-cell-autonomous tumor suppression by p53 |
| Abstract: | 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. © 2013 Elsevier Inc. |
| Journal Title: | Cell |
| Volume: | 153 |
| Issue: | 2 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2013-04-11 |
| Start Page: | 449 |
| End Page: | 460 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 23562644 |
| DOI: | 10.1016/j.cell.2013.03.020 |
| PMCID: | PMC3702034 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2013" - "CODEN: CELLB" - ":doi 10.1016/j.cell.2013.03.020" - "Source: Scopus" |
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