Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Oncogenic RUNX3: A Link between p53 Deficiency and MYC Dysregulation

  • Date, Yuki (Department of Molecular Bone Biology, Graduate School of Biomedical Sciences, Nagasaki University) ;
  • Ito, Kosei (Department of Molecular Bone Biology, Graduate School of Biomedical Sciences, Nagasaki University)
  • Received : 2019.11.24
  • Accepted : 2019.12.12
  • Published : 2020.02.29
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Abstract

The RUNX transcription factors serve as master regulators of development and are frequently dysregulated in human cancers. Among the three family members, RUNX3 is the least studied, and has long been considered to be a tumor-suppressor gene in human cancers. This idea is mainly based on the observation that RUNX3 is inactivated by genetic/epigenetic alterations or protein mislocalization during the initiation of tumorigenesis. Recently, this paradigm has been challenged, as several lines of evidence have shown that RUNX3 is upregulated over the course of tumor development. Resolving this paradox and understanding how a single gene can exhibit both oncogenic and tumor-suppressive properties is essential for successful drug targeting of RUNX. We propose a simple explanation for the duality of RUNX3: p53 status. In this model, p53 deficiency causes RUNX3 to become an oncogene, resulting in aberrant upregulation of MYC.

Keywords

References

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  2. Runx Transcription Factors in T Cells-What Is Beyond Thymic Development? vol.12, 2020, https://doi.org/10.3389/fimmu.2021.701924
  3. Runx3 Induces a Cell Shape Change and Suppresses Migration and Metastasis of Melanoma Cells by Altering a Transcriptional Profile vol.22, pp.4, 2020, https://doi.org/10.3390/ijms22042219
  4. Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression vol.11, 2021, https://doi.org/10.3389/fonc.2021.725336
  5. Small peptide inhibitor from the sequence of RUNX3 disrupts PAK1-RUNX3 interaction and abrogates its phosphorylation-dependent oncogenic function vol.40, pp.34, 2020, https://doi.org/10.1038/s41388-021-01927-x