title: Myc coordinates transcription and translation to enhance transformation and suppress invasiveness.
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.
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands r.agami@nki.nl r.elkon@nki.nl.
authors.forename: Ran
authors.initials: R
authors.lastname: Elkon
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Loayza-Puch
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Gozde
authors.initials: G
authors.lastname: Korkmaz
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Rui
authors.initials: R
authors.lastname: Lopes
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: van Breugel
authors.affiliation: Mass Spectrometry/Proteomics Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Onno B
authors.initials: OB
authors.lastname: Bleijerveld
authors.affiliation: 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.
authors.forename: A F Maarten
authors.initials: AF
authors.lastname: Altelaar
authors.affiliation: Biozentrum der Universität Würzburg Theodor Boveri Institut Am Hubland, Würzburg, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Biozentrum der Universität Würzburg Theodor Boveri Institut Am Hubland, Würzburg, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lorenzin
authors.affiliation: Biozentrum der Universität Würzburg Theodor Boveri Institut Am Hubland, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.affiliation: 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.
authors.forename: Reuven
authors.initials: R
authors.lastname: Agami
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: c‐Myc; metastasis; transcriptional responses; transformation; translational regulation