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

Myc coordinates transcription and translation to enhance transformation and suppress invasiveness.

Author information

1
Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands r.agami@nki.nl r.elkon@nki.nl.
2
Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Mass Spectrometry/Proteomics Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
4
Mass Spectrometry/Proteomics Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht, The Netherlands Netherlands Proteomics Centre Cancer Genomics Centre, Utrecht, The Netherlands.
5
Biozentrum der Universität Würzburg Theodor Boveri Institut Am Hubland, Würzburg, Germany.
6
Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands Erasmus MC, Rotterdam University, Rotterdam, The Netherlands r.agami@nki.nl r.elkon@nki.nl.

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

PMID:
26538417
PMCID:
PMC4687422
DOI:
10.15252/embr.201540717
[Indexed for MEDLINE]
Free PMC Article

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