Regulation of self-renewal in normal and cancer stem cells

Maria V. Verga Falzacappa, Chiara Ronchini, Linsey B. Reavie, Pier G. Pelicci

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations can confer a selective advantage on specific cells, enabling them to go through the multistep process that leads to malignant transformation. The cancer stem cell hypothesis postulates that only a small pool of low-cycling stem-like cells is necessary and sufficient to originate and develop the disease. Normal and cancer stem cells share important functional similarities such as 'self-renewal' and differentiation potential. However, normal and cancer stem cells have different biological behaviours, mainly because of a profound deregulation of self-renewal capability in cancer stem cells. Differences in mode of division, cell-cycle properties, replicative potential and handling of DNA damage, in addition to the activation/inactivation of cancer-specific molecular pathways confer on cancer stem cells a malignant phenotype. In the last decade, much effort has been devoted to unravel the complex dynamics underlying cancer stem cell-specific characteristics. However, further studies are required to identify cancer stem cell-specific markers and targets that can help to confirm the cancer stem cell hypothesis and develop novel cancer stem cell-based therapeutic approaches. It has been shown that only a small sub-population of cells, the cancer stem cells (CSCs), is necessary and sufficient to originate a tumour. We discuss how, compared to normal SCs, CSCs exhibit a profound de-regulation of their self-renewal capability, mainly due to differences in mode of division, cell-cycle properties, replicative potential and handling of DNA-damage.

Original languageEnglish
Pages (from-to)3559-3572
Number of pages14
JournalFEBS Journal
Volume279
Issue number19
DOIs
Publication statusPublished - Oct 2012

Keywords

  • asymmetric division
  • cancer stem cell
  • cancer therapy
  • DNA damage
  • genomic instability
  • p21
  • p53
  • self-renewal
  • stem cell
  • symmetric division

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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