Inhibitor of DNA-binding 4 contributes to the maintenance and expansion of cancer stem cells in 4T1 mouse mammary cancer cell line.

The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer. CSC-targeted therapies may prevent cancer relapse and provide more effective treatment. The expression of aldehyde dehydrogenase 1, as assessed by the Aldefluor assay, has been recognized as a marker of CSCs in breast cancer. Inhibitors of DNA-binding proteins (IDs) have an important role in stem cell differentiation. In this study, we examined IDs necessary for the regulation of stem properties in Aldefluor(pos) 4T1 cells. When the expression profile of IDs in Aldefluor(neg) and Aldefluor(pos) 4T1 cells was compared, qRT-PCR analysis showed that ID4 expression was highly upregulated in Aldefluor(pos) 4T1 cells. In addition, knockdown of ID4 expression suppressed the properties of CSCs, including their sphere-forming ability and side population phenotype. The findings suggest that ID4 may be a therapeutic target for the treatment of advanced breast cancer.