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The RUNX Genes as Conditional Oncogenes: Insights from Retroviral Targeting and Mouse Models

James C Neil1, Kathryn Gilroy2, Gillian Borland2

  • 1Molecular Oncology Laboratory, Centre for Virus Research, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK. James.Neil@glasgow.ac.uk.

Advances in Experimental Medicine and Biology
|March 17, 2017
PubMed

Insights

Runx genes are conditional oncogenes, acting as growth inhibitors unless combined with MYC overexpression or p53 loss. Their dual role in cancer, promoting or suppressing, depends on cancer stage and specific gene interactions.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Runx genes were initially identified as dominant oncogenes but are now understood as conditional oncogenes.
  • Overexpression of Runx genes can inhibit growth unless other genetic events occur, such as MYC overexpression or p53 loss.

Purpose of the Study:

  • To elucidate the conditional oncogenic role of Runx genes in cancer development and progression.
  • To reconcile apparently conflicting roles of Runx genes in cancer suppression and promotion.
  • To investigate the functional redundancy of Runx genes in cancer.

Main Methods:

  • Analysis of retroviral insertion data to identify Runx gene targets.
  • Investigation of gene interactions, including MYC, p53, and Ras, in the context of Runx gene activity.
  • Examination of endogenous Runx activity in MYC-driven lymphoma cells.
  • Review of evidence for RUNX gene involvement in human cancers.

Main Results:

  • Runx and MYC co-overexpression neutralizes p53 tumor suppression through unknown mechanisms.
  • Basal RUNX activity is crucial for the viability and proliferation of MYC-driven lymphoma cells.
  • Human RUNX genes are overexpressed in advanced cancers, suggesting a conditional oncogenic role.
  • Reduced RUNX activity can paradoxically promote cell immortalization and transformation, especially with mutant Ras.

Conclusions:

  • Runx genes exhibit context-dependent roles in cancer, acting as promoters or suppressors based on cellular events and cancer stage.
  • A stage-specific model may reconcile the diverse functions of Runx genes in tumorigenesis.
  • Further research is needed to determine the functional redundancy of the three Runx genes in cancer.
Keywords:
CancerLymphomaOncogeneRetroviral mutagenesisSenescenceTumour suppressor

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