Transcription factor Runx2 changes the expression of some matricellular proteins in metastatic breast cancer cells

Abstract

Background Runx2 is one of the runt-related genes that are overexpressed in human cancers and contribute to metastasis. The cancer cell metastasis requires modifications of the extracellular matrix (ECM) and reduction in ECM-cell interaction. This process is performed by various enzymes and proteins secreted by cancer and surrounding cells. This study aimed to investigate the effect of the Runx2 transcription factor on the expression of matricellular proteins such as HPA1, LOX, SPARC, and OPN, which have important roles in ECM modification and ECM-cell interaction in human breast cancer. Also, the changes in their associated oncogenic pathways including Akt, Erk, FAK activities, and c-jun protein expression were investigated. Methods and results Runx2 knockdown model was created using runx2 siRNA in MDA-MB-231 human metastatic breast cancer cells. The changes in the mRNA and protein expressions of ECM proteins were shown by the qPCR and Western blotting, respectively. The results showed that there was a decrease in both mRNA and protein expressions of HPA1, SPARC, and LOX, whereas there was no change in those of OPN. Phosphorylated Akt, Erk, FAK levels, and protein expression of c-jun, however, decreased in the cells. Conclusion Our results revealed that Runx2 affected matricellular protein expression, which is important for metastasis and invasion of breast cancer. Hence, we have concluded that runx2 appears to be efficient for regulating breast cancer metastasis through an expression of matricellular proteins.