Myc coordinates transcription and translation to enhance transformation and suppress invasiveness

EMBO Rep. 2015 Dec;16(12):1723-36. doi: 10.15252/embr.201540717. Epub 2015 Nov 4.

Abstract

c-Myc is one of the major human proto-oncogenes and is often associated with tumor aggression and poor clinical outcome. Paradoxically, Myc was also reported as a suppressor of cell motility, invasiveness, and metastasis. Among the direct targets of Myc are many components of the protein synthesis machinery whose induction results in an overall increase in protein synthesis that empowers tumor cell growth. At present, it is largely unknown whether beyond the global enhancement of protein synthesis, Myc activation results in translation modulation of specific genes. Here, we measured Myc-induced global changes in gene expression at the transcription, translation, and protein levels and uncovered extensive transcript-specific regulation of protein translation. Particularly, we detected a broad coordination between regulation of transcription and translation upon modulation of Myc activity and showed the connection of these responses to mTOR signaling to enhance oncogenic transformation and to the TGFβ pathway to modulate cell migration and invasiveness. Our results elucidate novel facets of Myc-induced cellular responses and provide a more comprehensive view of the consequences of its activation in cancer cells.

Keywords: c‐Myc; metastasis; transcriptional responses; transformation; translational regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc
  • Humans
  • Neoplasm Invasiveness*
  • Neoplasm Metastasis / genetics*
  • Neoplasms / genetics*
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • MTOR protein, human
  • TOR Serine-Threonine Kinases

Associated data

  • GEO/GSE66929