Gene Transactivation and Transrepression in MYC-Driven Cancers

Int J Mol Sci. 2021 Mar 27;22(7):3458. doi: 10.3390/ijms22073458.

Abstract

MYC is a proto-oncogene regulating a large number of genes involved in a plethora of cellular functions. Its deregulation results in activation of MYC gene expression and/or an increase in MYC protein stability. MYC overexpression is a hallmark of malignant growth, inducing self-renewal of stem cells and blocking senescence and cell differentiation. This review summarizes the latest advances in our understanding of MYC-mediated molecular mechanisms responsible for its oncogenic activity. Several recent findings indicate that MYC is a regulator of cancer genome and epigenome: MYC modulates expression of target genes in a site-specific manner, by recruiting chromatin remodeling co-factors at promoter regions, and at genome-wide level, by regulating the expression of several epigenetic modifiers that alter the entire chromatin structure. We also discuss novel emerging therapeutic strategies based on both direct modulation of MYC and its epigenetic cofactors.

Keywords: MYC; MYC deregulation; MYC-driven cancers; epigenetic modulation; therapeutic target; therapy resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis
  • Cell Differentiation
  • Cell Proliferation
  • Chromatin / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Epigenesis, Genetic
  • Epigenome
  • Gene Expression Regulation, Neoplastic*
  • Genome, Human
  • Hematopoietic Stem Cells / cytology
  • Homeostasis
  • Humans
  • Kruppel-Like Transcription Factors / metabolism
  • Leukemia / metabolism
  • Lymphoma / metabolism
  • Neoplasms / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Signal Transduction
  • Stem Cells / metabolism
  • Transcription Factors / metabolism
  • Transcriptional Activation*

Substances

  • CDKN1B protein, human
  • Chromatin
  • Kruppel-Like Transcription Factors
  • MAS1 protein, human
  • MYC protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • ZBTB17 protein, human
  • Cyclin-Dependent Kinase Inhibitor p27