Role of RUNX2 in breast cancer development and drug resistance (Review)

Abstract

Breast cancer is the most common malignancy and ranks second among the causes of tumor-associated death in females. The recurrence and drug resistance of breast cancer are intractable due to the presence of breast cancer stem cells (BCSCs), which are adequate to initiate tumor formation and refractory to conventional remedies. Runt-related transcription factor 2 (RUNX2), a pivotal transcription factor in mammary gland and bone development, has also been related to metastatic cancer and BCSCs. State-of-the-art research has indicated the retention of RUNX2 expression in a more invasive subtype of breast cancer, and in particular, triple-negative breast cancer development and drug resistance are associated with estrogen receptor signaling pathways. The present review mainly focused on the latest updates on RUNX2 in BCSCs and their roles in breast cancer progression and drug resistance, providing insight that may aid the development of RUNX2-based diagnostics and treatments for breast cancer in clinical practice.

Keywords: RUNX2; breast cancer; drug resistance; regulatory mechanism; stem cells.

Figure 1.

Schematic diagram of possible drug resistance mechanisms of RUNX2 in breast cancer. In breast cancer, aberrant RUNX2 expression contributes to drug resistance. Elevated serum miR-4530 levels may sensitize breast cancer to drugs by suppressing RUNX2. The drug resistance of breast cancer may be initiated by the direct transcription of SOX9 induced by the interaction of RUNX2 with ERα. In addition, RUNX2 may regulate BCSCs, which cause drug resistance through protein ABCG2 or the PI3K and NRF2 signaling pathways. ROS in BCSCs also have a certain role. Finally, RUNX2 may affect EMT through secreted protein MMP1 or signaling pathways, such as TGF-β and Wnt, and EMT regulates BCSCs and eventually leads to breast cancer resistance. RUNX2, Runt-related transcription factor 2; miR, microRNA; ER, estrogen receptor; NRF2, nuclear factor erythroid 2-related factor 2; BCSC, breast cancer stem cell; ROS, reactive oxygen species; ABCG2, ATP binding cassette subfamily G member 2; EMT, epithelial to mesenchymal transition.