Runt-related transcription factors in human carcinogenesis: a friend or foe?

Abstract

Purpose: Cancer is one of the deadliest pathologies with more than 19 million new cases and 10 million cancer-related deaths across the globe. Despite development of advanced therapeutic interventions, cancer remains as a fatal pathology due to lack of early prognostic biomarkers, therapy resistance and requires identification of novel drug targets.

Methods: Runt-related transcription factors (Runx) family controls several cellular and physiological functions including osteogenesis. Recent literatures from PubMed was mined and the review was written in comprehensive manner RESULTS: Recent literature suggests that aberrant expression of Runx contributes to tumorigenesis of many organs. Conversely, cell- and tissue-specific tumor suppressor roles of Runx are also reported. In this review, we have provided the structural/functional properties of Runx isoforms and its regulation in context of human cancer. Moreover, in an urgent need to discover novel therapeutic interventions against cancer, we comprehensively discussed the reported oncogenic and tumor suppressive roles of Runx isoforms in several tumor types and discussed the discrepancies that may have risen on Runx as a driver of malignant transformation.

Conclusion: Runx may be a novel therapeutic target against a battery of deadly human cancers.

Keywords: Cancer therapeutics; Runt-related transcription factor; Signal transduction; Tumorigenesis.

Fig. 1

Structural properties and genetic alterations of Runx isoforms in human cancers. A Genetic and protein structures of all three Runx isoforms are mentioned. The downward arrow indicates the start ATG codon derived from P1 and P2 transcripts. Transactivation Domain (TAD) and exons are shown in light and dark green colors respectively. The Untranslated Regions (UTRs) are represented by white, while alternate splicing and dominant splicing are depicted by dashed and solid lines respectively. The conserved domains of the protein structures of Runx are indicated as the Runt Homology Domain (RHD), Nuclear Localization Signals (NLS), Inhibitory (ID), Transactivation (AD), C-terminal Groucho/TLE-binding site (VWRPY), and the RUNX2-specific glutamine/alanine-rich (QA) sequence. B, C Genetic alterations including gene amplification, mutations and structural variations in RUNX1-3 in human cancers are shown (TCGA)

Fig. 2

Expression and summarized molecular mechanisms of Runx isoforms in human cancer. A Expression of Runx1-3 in designated human cancer cell lines is shown (Human Protein Atlas). B Expression of Runx1-3 in designated human cancer patient tissue samples is analyzed by immunohistochemistry (Human Protein Atlas). C Summarized molecular mechanisms of Runx isoforms as both oncogenes and tumor suppressors are shown. D Aberrant expressions of specific Runx isoforms in several human cancers are shown