4.7 Article

Myc coordinates transcription and translation to enhance transformation and suppress invasiveness

期刊

EMBO REPORTS
卷 16, 期 12, 页码 1723-1736

出版社

WILEY
DOI: 10.15252/embr.201540717

关键词

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

资金

  1. Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BD/74476/2010]
  2. Netherlands Organization for Scientific Research (NWO), National Roadmap Large-scale Research Facilities of the Netherlands [184.032.201]
  3. Dutch Cancer Society (KWF)
  4. VICI program of the NWO
  5. European Research Council (ERC) Advanced Grant EnhReg
  6. NWO through a VIDI grant [723.012.102]
  7. Fundação para a Ciência e a Tecnologia [SFRH/BD/74476/2010] Funding Source: FCT

向作者/读者索取更多资源

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 TGF beta 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.

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