RUNX family: Oncogenes or tumor suppressors (Review)

Abstract

Runt‑related transcription factor (RUNX) proteins belong to a transcription factors family known as master regulators of important embryonic developmental programs. In the last decade, the whole family has been implicated in the regulation of different oncogenic processes and signaling pathways associated with cancer. Furthermore, a suppressor tumor function has been also reported, suggesting the RUNX family serves key role in all different types of cancer. In this review, the known biological characteristics, specific regulatory abilities and experimental evidence of RUNX proteins will be analyzed to demonstrate their oncogenic potential and tumor suppressor abilities during oncogenic processes, suggesting their importance as biomarkers of cancer. Additionally, the importance of continuing with the molecular studies of RUNX proteins' and its dual functions in cancer will be underlined in order to apply it in the future development of specific diagnostic methods and therapies against different types of cancer.

Figure 1.

RUNX family genomic and protein structure. The diagram represents the position of several motifs in RUNX family genes. White boxes represent noncoding exons and shaded boxes coding exons. Figure adapted from Fig. 2 in reference (44). RUNX, runt-related transcription factor.

Figure 2.

Two RUNX1 fusion proteins and their role in carcinogenesis. RUNX1 alters its normal molecular action by forming different complexes (RUNX1-ETO, TEL-RUNX1), and activating and/or inhibiting specific groups of genes. Figure adapted from Fig. 8 in reference (114) and Fig. 5 in reference (89). RUNX, runt-related transcription factor.

Figure 3.

Signaling pathways related to RUNX1. RUNX1 has been involved in NF-κB pathway. Figure adapted from Fig. 2 in reference (7), Fig. 2 in reference (60), Fig. 2 in reference (167) and Fig. 2 in reference (168). RUNX, runt-related transcription factor.

Figure 4.

Signaling pathways related to RUNX2. RUNX2 has been involved with TGF-β pathway. Figure adapted from Fig. 2 in reference (172), Fig. 2 in reference (167), Fig. 2 in reference (7), Fig. 4 in reference (173), Fig. 1 in reference (174) and Fig. 2 in reference (175). RUNX, runt-related transcription factor.

Figure 5.

Signaling pathways related to RUNX3. RUNX3 has been involved with TGF-β pathway. Figure adapted from Figs. 1, 2 and 3 in reference (184). RUNX, runt-related transcription factor.