CANCER Final act of senescence

Spanish National Cancer Research Centre (CNIO), Madrid E28029, Spain.
Nature (Impact Factor: 41.46). 11/2011; 479(7374):481-2. DOI: 10.1038/479481a
Source: PubMed


Damaged cells can initiate cancer. To avert this, faulty cells disable
their own propagation by undergoing senescence. But for full protection
against liver cancer, the senescent cells must be cleared by the immune
system. See Letter p.547

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    • "2013 ) . Paracrine effects of the SASP also provoke anti - tumor immunity ( Serrano 2011 ; Hoenicke and Zender 2012 ) . "
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    ABSTRACT: Cellular senescence is a stress response that accompanies stable exit from the cell cycle. Classically, senescence, particularly in human cells, involves the p53 and p16/Rb pathways, and often both of these tumor suppressor pathways need to be abrogated to bypass senescence. In parallel, a number of effector mechanisms of senescence have been identified and characterized. These studies suggest that senescence is a collective phenotype of these multiple effectors, and their intensity and combination can be different depending on triggers and cell types, conferring a complex and diverse nature to senescence. Series of studies on senescence-associated secretory phenotype (SASP) in particular have revealed various layers of functionality of senescent cells in vivo. Here we discuss some key features of senescence effectors and attempt to functionally link them when it is possible.
    Genes & development 01/2014; 28(2):99-114. DOI:10.1101/gad.235184.113 · 10.80 Impact Factor
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    • "The question then arises: Why do senescent cells which do not proliferate, pose a cancer risk and require elimination? This raises the possibility that at least a proportion of these cells can revert from terminal senescence [11]. In this article we review the recent evidence supporting this possibility and provide a hypothesis for the molecular and biological basis for how reversion may occur through induced polyploidy and reprogramming for totipotency. "
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    ABSTRACT: Metastatic cancer is rarely cured by current DNA damaging treatments, apparently due to the development of resistance. However, recent data indicates that tumour cells can elicit the opposing processes of senescence and stemness in response to these treatments, the biological significance and molecular regulation of which is currently poorly understood. Although cellular senescence is typically considered a terminal cell fate, it was recently shown to be reversible in a small population of polyploid cancer cells induced after DNA damage. Overcoming genotoxic insults is associated with reversible polyploidy, which itself is associated with the induction of a stemness phenotype, thereby providing a framework linking these separate phenomena. In keeping with this suggestion, senescence and autophagy are clearly intimately involved in the emergence of self-renewal potential in the surviving cells that result from de-polyploidisation. Moreover, subsequent analysis indicates that senescence may paradoxically be actually required to rejuvenate cancer cells after genotoxic treatments. We propose that genotoxic resistance is thereby afforded through a programmed life-cycle-like process which intimately unites senescence, polyploidy and stemness.
    Cancer Cell International 09/2013; 13(1):92. DOI:10.1186/1475-2867-13-92 · 2.77 Impact Factor
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    • "Age is an independent risk factor for poor outcome in primary biliary cirrhosis (PBC) in addition to the presence of portal hypertension and impaired liver function [66-68]. It has been hypothesized that the increased susceptibility of aging people to neoplastic diseases are due to a decrease in basic immune defense functions [39,69]. "
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    ABSTRACT: It has now ascertained that the clinical manifestations of liver disease in the elderly population reflect both the cumulative effects of longevity on the liver and the generalized senescence of the organism ability to adjust to metabolic, infectious, and immunologic insults. Although liver tests are not significantly affected by age, the presentation of liver diseases such as viral hepatitis may be subtler in the elderly population than that of younger patients. Human immunosenescence is a situation in which the immune system, particularly T lymphocyte function, deteriorates with age, while innate immunity is negligibly affected and in some cases almost up-regulated. We here briefly review the relationships between the liver aging process and mast cells, the key effectors in a more complex range of innate immune responses than originally though.
    Immunity & Ageing 03/2013; 10(1):9. DOI:10.1186/1742-4933-10-9 · 3.54 Impact Factor
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