Abstract
Runt-related transcription factor 2 (RUNX2) is critical for the modulation of chondrocyte osteoblast differentiation and hypertrophy. Recently discovered RUNX2 somatic mutations, expressional signatures of RUNX2 in normal tissues and tumors, and the prognostic and clinical significance of RUNX2 in many types of cancer have attracted attention and led RUNX2 to be considered a biomarker for cancer. Many discoveries have illustrated the indirect and direct biological functions of RUNX2 in orchestrating cancer stemness, cancer metastasis, angiogenesis, proliferation, and chemoresistance to anticancer compounds, warranting further exploration of the associated mechanisms to support the development of a novel therapeutic strategy. In this review, we focus mainly on critical and recent research developments, including RUNX2's oncogenic activities, by summarizing and integrating the findings on somatic mutations of RUNX2, transcriptomic studies, clinical information, and discoveries about how the RUNX2-induced signaling pathway modulates malignant progression in cancer. We also comprehensively discuss RUNX2 RNA expression in a pancancer panel and in specific normal cell types at the single-cell level to indicate the potential cell types and sites for tumorigenesis. We expect this review to shed light on the recent mechanistical findings and modulatory role of RUNX2 in cancer progression and provide biological information that can guide new research in this field.