Oncogenic MYC amplifies mitotic perturbations

Samantha Littler1, Olivia Sloss1, Bethany Geary1,2

  • 1Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Cancer Research Centre, 555 Wilmslow Road, Manchester M20 4GJ, UK.

Open Biology
|August 29, 2019
PubMed

Insights

The oncogenic transcription factor MYC affects cell division, leading to chromosome instability. MYC

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Genetics

Background:

  • The transcription factor MYC is a key regulator of cellular processes.
  • MYC deregulation contributes to genomic instability and cancer.
  • The precise mechanisms by which MYC influences mitosis remain unclear.

Purpose of the Study:

  • To investigate how deregulated MYC impacts mitotic chromosome segregation.
  • To elucidate the role of MYC in driving chromosome instability during mitosis.

Main Methods:

  • Overexpression of MYC in cells.
  • Analysis of mitotic spindle morphology and chromosome alignment.
  • Assessment of mitotic anomalies and micronuclei formation.
  • Proteomic analysis to identify MYC-interacting partners and pathways.
  • Investigation of MYC's effect on Polo-like kinase 1 (PLK1) activity.

Main Results:

  • MYC overexpression alters spindle morphology and chromosome dynamics during mitosis.
  • Cells with MYC overexpression exhibit increased sensitivity to anti-mitotic drugs, leading to more micronuclei.
  • Proteomic analysis identified PLK1 as a central hub modulated by MYC.
  • MYC influences PLK1-dependent processes including mitotic entry, spindle assembly, and spindle assembly checkpoint (SAC) satisfaction.

Conclusions:

  • Deregulated MYC significantly impacts multiple aspects of mitosis and chromosome segregation.
  • MYC's modulation of PLK1-dependent pathways provides a mechanistic link to MYC-driven chromosome instability.
  • These findings highlight MYC's pervasive role in promoting genomic instability in cancer.

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