RUNX2 and Osteosarcoma

Osteosarcoma (OS) is the most common pediatric bone cancer in children and young adults. Previous studies have suggested the importance of osteoblast activity in OS tumorigenesis and metastasis, as OS is characterized by abnormal bone formation, while osteoblast is the predominant cell type both in OS and in metastatic tumor tissues. RUNX2 is a known essential transcription factor for osteoblast differentiation. RUNX2 has also been linked to many human cancers, including bone cancers and cancer metastasis in bone. However, the view of RUNX2 during OS tumorigenesis has not been unanimous. In this manuscript, we reviewed the osteoblastic origin in OS etiology. The oncogenic property of RUNX2 in human OS studies was briefly summarized. RUNX2 may be involved in OS pathogenesis by regulating cell cycle controlling of (pre)-osteoblasts, which subsequently convert to OS cells. The roles and mechanisms of RUNX2 during OS metastasis and bone metastasis in target cancers (herein prostate and breast cancers), were as described. The potential involvement of Runx2 in multiple mouse OS models that use human OS cell lines (Xenografts), tumor suppressor genes p53 and Rb1 were also discussed. Finally, we updated some microRNAs studies and their relation with RUNX2 in OS pathogenesis. This review provides a comprehensive understanding of RUNX2's function during OS pathogenesis and will help with the research designing and strategy in controlling OS.