Transcription factor FOXP2 attenuates the stemness of breast cancer cells by abolishing the transcription of Twist1.

Transcription factor FOXP2 participates in language acquisition and increasing evidence suggests that dysregulation of FOXP2 is associated with human tumorigenesis and progression. Reducing FOXP2 levels has increased breast cancer stem cell viability, but its inhibitory mechanisms to cancer stem cells are still not fully understood. In this study, we found that the expression levels of FOXP2 were downregulated in clinical breast cancers and negatively correlated with the cancer stem cell marker ALDH1. We demonstrated that the expression of FOXP2 was significantly decreased in the mammosphere formed by breast cancer cells. The overexpression of FOXP2 reduced the expression of cancer stem cell markers and consequently the mammosphere formation ability in breast cancer cells. We found that FOXP2 directly inhibited the transcription of Twist1, a proto-oncogene promoting the metastasis and stemness of cancer cells. The compensatory expression of Twist1 in FOXP2-overexpressing breast cancer cells counteracted FOXP2's inhibitory effects on the stemness of breast cancer cells. Together, the results showed that FOXP2 attenuated the stemness of breast cancer cells by abolishing the transcription of Twist1.