Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology

Krizhanovsky, V., Xue, W., Zender, L., Yon, M., Hernando, E., Lowe, S. W. (2008) Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. Cold Spring Harb Symp Quant Biol, 73. pp. 513-22.

URL: http://www.ncbi.nlm.nih.gov/pubmed/19150958
DOI: 10.1101/sqb.2008.73.048

Abstract

Cellular senescence is characterized by an irreversible cell cycle arrest that, when bypassed by mutation, contributes to cellular immortalization. Activated oncogenes induce a hyperproliferative response, which might be one of the senescence cues. We have found that expression of such an oncogene, Akt, causes senescence in primary mouse hepatoblasts in vitro. Additionally, AKT-driven tumors undergo senescence in vivo following p53 reactivation and show signs of differentiation. In another in vivo system, i.e., liver fibrosis, hyperproliferative signaling through AKT might be a driving force of the senescence in activated hepatic stellate cells. Senescent cells up-regulate and secrete molecules that, on the one hand, can reinforce the arrest and, on the other hand, can signal to an innate immune system to clear the senescent cells. The mechanisms governing senescence and immortalization are overlapping with those regulating self-renewal and differentiation. These respective control mechanisms, or their disregulation, are involved in multiple pathological conditions including fibrosis, wound healing, and cancer. Understanding extracellular cues that regulate these processes may enable new therapies for these conditions.

Item Type: Paper
Uncontrolled Keywords: 1-Phosphatidylinositol 3-Kinase/metabolism Animals *Cell Aging/genetics/physiology Cell Proliferation Cell Transformation, Neoplastic Gene Expression Genes, p53 Hepatic Stellate Cells/cytology/immunology/metabolism Humans Immunity, Innate Liver Cirrhosis/metabolism/pathology/prevention & control Liver Neoplasms, Experimental/genetics/pathology Mice Neoplasms/genetics/*pathology Oncogene Protein v-akt/genetics/metabolism Oncogenes Signal Transduction Stem Cells/*cytology/metabolism Wound Healing
Subjects: diseases & disorders > cancer
diseases & disorders
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
therapies > stem cells
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: 2008
Date Deposited: 26 Feb 2013 17:29
Last Modified: 26 Feb 2013 17:29
PMCID: PMC3285266
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27549

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