Title |
Non-Cell-Autonomous Tumor Suppression by p53
|
---|---|
Published in |
Cell, April 2013
|
DOI | 10.1016/j.cell.2013.03.020 |
Pubmed ID | |
Authors |
Amaia Lujambio, Leila Akkari, Janelle Simon, Danielle Grace, Darjus F. Tschaharganeh, Jessica E. Bolden, Zhen Zhao, Vishal Thapar, Johanna A. Joyce, Valery Krizhanovsky, Scott W. Lowe |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 29% |
United Kingdom | 2 | 29% |
Australia | 1 | 14% |
Unknown | 2 | 29% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 86% |
Practitioners (doctors, other healthcare professionals) | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | <1% |
Portugal | 3 | <1% |
United Kingdom | 3 | <1% |
Japan | 3 | <1% |
France | 2 | <1% |
Germany | 2 | <1% |
Canada | 2 | <1% |
Austria | 1 | <1% |
Belgium | 1 | <1% |
Other | 6 | <1% |
Unknown | 662 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 190 | 28% |
Researcher | 125 | 18% |
Student > Master | 66 | 10% |
Student > Bachelor | 54 | 8% |
Student > Doctoral Student | 46 | 7% |
Other | 88 | 13% |
Unknown | 120 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 209 | 30% |
Biochemistry, Genetics and Molecular Biology | 182 | 26% |
Medicine and Dentistry | 84 | 12% |
Immunology and Microbiology | 18 | 3% |
Chemistry | 14 | 2% |
Other | 42 | 6% |
Unknown | 140 | 20% |