Cellular senescence and tumor promotion: Is aging the key?

Natalia Loaiza, Marco Demaria*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

54 Citations (Scopus)

Abstract

The senescence response is a potent tumor suppressor mechanism characterized by an irreversible growth arrest in response to potentially oncogenic signals to prevent the proliferation of damaged cells. Late in life, some of the features of senescent cells seem to mediate the development of age-related pathologies, including cancer. In the present review, we present a summary of the current knowledge regarding the causes, effector pathways and cellular features of senescence. We also discuss how the senescence response, initially a tumor suppressor mechanism, turns into a tumor promoter apparently as a consequence of aging. We argue that three age-related phenomena-senescence-associated secretory phenotype (SASP) dysregulation, decline in the immune system function and genomic instability-could contribute, independently or synergistically, to deteriorate the efficacy of the senescence response in stopping cancer. As a consequence, senescent cells could be considered premalignant cells, and targeting senescent cells could be a preventive and therapeutic strategy against cancer.

Original languageEnglish
Pages (from-to)155-167
Number of pages13
JournalBiochimica et biophysica acta-Reviews on cancer
Volume1865
Issue number2
Early online date2-Feb-2016
DOIs
Publication statusPublished - Apr-2016

Keywords

  • Aging
  • Cancer
  • Cellular senescence
  • Premalignant
  • Pseudo-senescence
  • SASP
  • ONCOGENE-INDUCED SENESCENCE
  • DAMAGE-RESPONSE ACTIVATION
  • DNA-DAMAGE
  • SECRETORY PHENOTYPE
  • HUMAN-CELLS
  • IN-VIVO
  • PREMATURE SENESCENCE
  • THERAPEUTIC OPPORTUNITIES
  • HOMOLOGOUS RECOMBINATION
  • HETEROCHROMATIN FOCI

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