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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)449-460
Number of pages12
Issue number2
StatePublished - 11 Apr 2013

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


Dive into the research topics of 'Non-cell-autonomous tumor suppression by p53'. Together they form a unique fingerprint.

Cite this