RUNX2 and Cancer

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.

Canine soft tissue sarcomas: the expression of RUNX2 and karyopherin alpha-2 in extraskeletal (soft tissues) and skeletal osteosarcomas

“…This also applies to extraskeletal osteosarcomas which frequently originate primarily from soft tissues, especially those of the mammary gland and manifest as poorly differentiated sarcomats, which are difficult to classify due to the absence of characterizing morphological features such as osteoid. Recent studies, such as that of Lin ( 10 ), also report on the critical role of RUNX2 in the dynamics of progression in different tumor types ( 16 ). It has been reported that RUNX2 may participate in the modulation of several key processes in cancer progression, including transdifferentiation and cancer stem cell potential, angiogenesis, proliferation and metastasis mechanisms, and potential drug resistance ( Figure 3 ).…”

“… RUNX2′s modulations to hallmarks of cancer [modified from Lin ( 10 )] and dysregulation of KPNA2 (overexpression) in promoting cancer cells [modified from Han and Wang ( 17 )]. …”

“…The same is true for RUNX2, an important transcription factor for skeletal development that is significantly involved in the activity of various bone cell components such as osteoblasts, multipotent mesenchymal cells, and chondrocytes ( 9 ). RUNX2 appears to be involved in many osteogenic and chondrogenic processes through the modulation of transcriptional activation and multiple signaling pathways ( 10 ). However, RUNX2 has also been identified as a potential co-factor in the biomolecular and genetic mechanisms that characterize tumorigenesis and neoplastic progression ( 11 ), through the modulation of mechanisms related to angiogenesis, metastasis, proliferation, cancer stemness and drug resistance ( 9 , 10 , 12 ).…”

“…RUNX2 appears to be involved in many osteogenic and chondrogenic processes through the modulation of transcriptional activation and multiple signaling pathways ( 10 ). However, RUNX2 has also been identified as a potential co-factor in the biomolecular and genetic mechanisms that characterize tumorigenesis and neoplastic progression ( 11 ), through the modulation of mechanisms related to angiogenesis, metastasis, proliferation, cancer stemness and drug resistance ( 9 , 10 , 12 ). The purpose of this original research work is to try to identify new biomolecular and immunohistochemical aspects of canine extraskeletal osteosarcoma, focusing in this case on the expression of the two main markers indicated, never considered in veterinary medicine for these rare forms of spontaneous soft tissue tumors.…”

The role of lncRNA HCG18 in human diseases

“…Runtrelated transcription factor 2 (RUNX2) is a well-known master regulator of osteoblast and chondrocyte differentiation, Latest findings suggest it promotes cancer progression by regulating cell proliferation, migration, and drug resistance. 124 Chen et al 47 found that HCG18 can upregulate the expression of RUNX2 by sponging miR-34a, thereby promoting the proliferation, migration and invasion of OS cells.…”