Epigenetic alterations associated with cellular senescence: a barrier against tumorigenesis or a red carpet for cancer?
Semin Cancer Biol
; 21(6): 360-6, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21946622
ABSTRACT
Cellular senescence is eminently characterized by a permanent cell cycle arrest and the acquisition of morphological, physiological and epigenetic changes. The establishment of cellular senescence can occur in response to telomere attrition associated with cell turnover and ageing or following oncogene activation. Although seemingly two distinct phenomena, cellular senescence and cancer share similarly altered global epigenetic profiles comprising changes in DNA methylation, involving global hypomethylation of repetitive DNA sequences and regional hypermethylation of some gene promoters, and in histone post-translational modifications. As epigenetic and genetic alterations are likely to act synergistically in cancer, anomalous epigenetic marks acquired during ageing or in response to oncogene activation might play important roles in tumorigenesis and cancer progression. These potentially tumor-promoting epigenetic alterations include transcriptional repression of genes encoding tumor suppressors or developmentally regulated proteins, expression of non-coding repetitive RNAs and acquisition of distinct heterochromatin marks that may contribute to suppress cell death by reducing DNA damage response. Cellular senescence may thus be viewed as a double-edged sword that, although acting as a potent anti-proliferative barrier, may pave the way to tumorigenesis in senescence-escaping cells by altering their epigenetic make up.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
/
Senescência Celular
/
Epigênese Genética
/
Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Semin Cancer Biol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Bélgica