Inhibition of cell differentiation: a critical mechanism for MYC-mediated carcinogenesis?

Javier Leon, Nuria Ferrandiz, Juan C Acosta, M Dolores Delgado

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Despite its early discovery and relevance in cancer, the mechanisms by which MYC brings about tumorigenic transformation have not been clarified. MYC elicits a variety of biological activities, the proliferation promotion being the best studied. However, inhibition of cell differentiation was one of the first MYC activities described. The importance of differentiation impairment in MYC-induced tumorigenesis is demonstrated in transgenic mice models with conditional MYC expression, where MYC inactivation leads to tumor regression associated to re-differentiation of tumor cells. To explain the anti-differentiation effects of MYC, it has been argued that MYC impairs differentiation by preventing exit from the cell cycle. However, we have described models where MYC blocks the erythroid or neuronal differentiation without reversing the proliferative arrest. In these and other models discussed here, MYC-mediated inhibition of differentiation occurs by blocking the upregulation of transcription factors that control the differentiation. The importance of MYC anti-differentiation function has recently gained importance after the discovery that MYC is one of the four transcription factors able to reprogram differentiated cells into pluripotent cells. We will discuss the hypothesis that MYC engages common pathways as a "stemness" keeper and as an oncogene.
Original languageEnglish
Pages (from-to)1148-57
Number of pages10
JournalCell Cycle
Issue number8
Publication statusPublished - 15 Apr 2009

Keywords / Materials (for Non-textual outputs)

  • Gene Expression Regulation, Neoplastic
  • Animals
  • Neoplasms
  • Humans
  • Cell Differentiation
  • Mice
  • Stem Cells
  • Cell Proliferation
  • Models, Biological
  • Proto-Oncogene Proteins c-myc


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