Inactivation of MYC reverses tumorigenesis

Y. Li, S. C. Casey, D. W. Felsher

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The MYC proto-oncogene is an essential regulator of many normal biological programmes. MYC, when activated as an oncogene, has been implicated in the pathogenesis of most types of human cancers. MYC overexpression in normal cells is restrained from causing cancer through multiple genetically and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis and cellular senescence. When pathologically activated in the correct epigenetic and genetic contexts, MYC bypasses these mechanisms and drives many of the 'hallmark' features of cancer, including uncontrolled tumour growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis and altered cellular metabolism. MYC also dictates tumour cell fate by enforcing self-renewal and by abrogating cellular senescence and differentiation programmes. Moreover, MYC influences the tumour microenvironment, including activating angiogenesis and suppressing the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can lead to the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumour regression associated with tumour cells undergoing proliferative arrest, differentiation, senescence and apoptosis, as well as remodelling of the tumour microenvironment, recruitment of an immune response and shutdown of angiogenesis. Hence, tumours appear to be addicted to the MYC oncogene because of both tumour cell intrinsic and host-dependent mechanisms. MYC is important for the regulation of both the initiation and maintenance of tumorigenesis.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalJournal of Internal Medicine
Volume276
Issue number1
DOIs
StatePublished - Jul 1 2014

Keywords

  • MYC Oncogene
  • Oncogene addiction
  • Targeted therapeutics
  • Transgenic mouse models

ASJC Scopus subject areas

  • Internal Medicine

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