Non-cell-autonomous tumor suppression by p53

Amaia Lujambio, Leila Akkari, Janelle Simo, Danielle Grace, Darjus F.Tschaharganeh, Jessica E.Bolden, Zhen Zhao, Vishal Thapar, Johanna A. Joyce, Valery Krizhanovsky, and Scott W. Lowe, Cell. 2013 April 11, 153, 449-460.

Speaker: Yun-chaio Ding (丁云喬)                            Time: 14:00~15:00, Dec. 11, 2013

Commentator: Dr. Bei-Chang Yang (楊倍昌 老師)    Place: Room 601

Abstract:

Within the cell growth progression, p53 is a crucial gene which could arrest the cell cycle. It is also called the tumor suppressor gene because its product can repress the malignant transformation of a damage cell to senescence or apoptosis. To reduce tumorigenesis, p53 also cooperate with the nuclear factor NF-κB for the senescence-associated secretory phenotype (SASP) in order to stabilize senescence properties. SASP can also act in an autonomous manner to arrest immune surveillance in damaged tissues, in which it will limit the extent of damage and facilitate wound resolution. In the presence of liver damage, ablation of p53-dependent senescence progression will stimulate the activation of hepatic stellate cell (HSC), leading to extracellular matrix secretion thus increase fibrosis and cirrhosis, which is associated with reduced survival by enhancing the progression carcinoma. P53-expression hepatic stellate cells interfere with the macrophage polarization, skewing them to become tumor-inhibition M1 type or tumor-promoting M2 type. The M1 or M2 macrophage will then secret cytokines to change the microenvironment to one that prefers or restricts tumor formation. Hence, p53 can not only autonomously control the cell phenotype but also non-cell autonomously affect their microenvironment.

References:

1          Tasdemir, N. & Lowe, S. W. Senescent cells spread the word: non-cell autonomous propagation of cellular senescence. The EMBO journal 32, 1975-1976, doi:10.1038/emboj.2013.139 (2013).

2          Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657-667, doi:10.1016/j.cell.2008.06.049 (2008).

3          Winau, F. et al. Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity 26, 117-129, doi:10.1016/j.immuni.2006.11.011 (2007).