The Effects Of RunX2 On Breast Cancer Stem Cells And Its Potential Mechanism

Breast cancer is one of the most common malignant tumors among women, with 1.7 million new cases and 0.5 million deaths every year all over the world. Recently, with the rapid progresses in the early diagnose and interventions, five-year survival rate of breast cancer has been greatly improved except the patients with distant metastases, whose five-year survival rate is only around 20%. Generally, distant metastases occur in about 30% of breast cancer patients, and 70% of distant metastases are bone metastases. The Invasive growth and distant metastases are the main causes of the failure of treatment and deaths of breast cancer. Numerous studies have demonstrated that breast cancer stem cells play an important role in the Invasive growth of breast cancer.Run X2, also called the core combined factor, is a member of runt gene family, which is an important transcription factor that participates in the differentiation of osteoblast marrow mesenchymal stem cells and the bone growth. Although there is evidence that Run X2 can affect the in vitro cultured mammary cell function, the role of Run X2 in normal breast development and breast cancer has not been clearly elucidated. Recently, even though most of the studies supported that Run X2 could enhance the ability of invasion and metastasis of breast cancer mainly through promoting proliferation, migration and invasion of breast cancer cells and angiogenesis, it is unclear whether Run X2 has an effect on breast cancer stem cells. Therefore, in this study, we investigated the effects and the underlying mechanisms of Run X2 in invasion and metastasis of breast cancer stem cells.We first examined the protein level of Run X2 and CD44 in normal breast cellsMCF-10 A and breast cancer cells MCF-7 and MB-231, and found that the protein level of Run X2 and CD44 in MCF-7 and MB-231 was increased, in comparison with that in MCF-10 A. Then we tested the proportion of CD44 and CD24, the surface marker of breast cancer stem cell, by flow cytometry, and found that there was a positive correlation between the expression of CD44, CD24 and Runx2. To further investigate whether the high expression of Runx2 can influence the biological behavior of breast cancer cells, we transfected Runx2 plasmid into MB-231 cells and found that the proportion of breast cancer stem cells was decreased in experimental group by flow cymetory assay. We also found that the transfection of Runx2 into MB-231 cells could inhibit the proliferation of breast cancer cells, the ability of invasion and the colony formation. In addition, the expression level of Runx2 and CD44 in clinical breast cancer tissue are closely correlated, which also positively related to the degree of malignant transformation. In summary, our results demonstrated that Runx2 up-regulated the proportion of breast cancer stem cell by promoting the proliferation, migration and invasion of breast cancer cells, which finally promoted the invasion and metastasis of breast cancer.