Myc coordinates transcription and translation to enhance transformation and suppress invasiveness

Ran Elkon*, Fabricio Loayza-Puch, Gozde Korkmaz, Rui Lopes, Pieter C. Van Breugel, Onno B. Bleijerveld, A. F Maarten Altelaar, Elmar Wolf, Francesca Lorenzin, Martin Eilers, Reuven Agami*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1723-1736
Number of pages14
JournalEMBO Reports
Volume16
Issue number12
DOIs
Publication statusPublished - 1 Dec 2015

Keywords

  • c-Myc
  • metastasis
  • transcriptional responses
  • transformation
  • translational regulation

Fingerprint

Dive into the research topics of 'Myc coordinates transcription and translation to enhance transformation and suppress invasiveness'. Together they form a unique fingerprint.

Cite this