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Review
. 2020 Feb 29;43(2):176-181.
doi: 10.14348/molcells.2019.0285.

Oncogenic RUNX3: A Link between p53 Deficiency and MYC Dysregulation

Yuki Date  1   2 , Kosei Ito  1
Affiliations
Review

Oncogenic RUNX3: A Link between p53 Deficiency and MYC Dysregulation

Yuki Date et al. Mol Cells. .

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: RUNX3; c-Myc; p53.

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Conflict of interest statement

Disclosure

The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. p53 status as a contextual determinant of the duality of RUNX3.
Following DNA damage or oncogenic stress, RUNX3 positively regulates p53 and is in turn suppressed by it; p53 then prevents tumorigenesis by decreasing the activity of crucial oncogenes such as MYC (left). Upon inactivation of p53, dysregulated RUNX3 starts to aberrantly upregulate MYC (right). Thus, p53 status is a contextual determinant for whether RUNX3 behaves as a tumor-suppressor or oncogene.
Fig. 2
Fig. 2. RUNX3 connects p53 deficiency and MYC dysregulation.
Are p53 deficiency and MYC dysregulation, two principal phenomena associated with tumor development, connected by RUNX3?
See this image and copyright information in PMC

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