Journal article

Non-cell-autonomous tumor suppression by p53.

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

Cell | Published : 2013

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 t..

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University of Melbourne Researchers