Reciprocal transrepression between FOXF2 and FOXQ1 controls basal-like breast cancer aggressiveness

FOXF2 and FOXQ1, forkhead box transcription factor superfamily members, are encoded by neighboring genes located on human chromosome 6p25.3 and play opposite roles in epithelial-mesenchymal transition (EMT) and metastasis in basal-like breast cancer (BLBC). However, the relationship between FOXF2 and FOXQ1 in cancer remains unknown. Here, we found mutual transcriptional repression between FOXF2 and FOXQ1, and the reciprocal negative feedback loop controlled EMT, aggressiveness, and chemoresistance in BLBC cells. We further demonstrated that FOXF2 recruited nuclear receptor corepressor 1 and histone deacetylase 3 to the FOXQ1 promoter to inhibit its transcription in BLBC cells, but FOXQ1 did not exert such an effect on FOXF2. Our findings reveal novel mechanisms underlying the determination of BLBC aggressiveness and the transrepressive function of FOXF2 in a basal-like cell subtype-specific manner. Therefore, blocking the vicious cycle of the abnormal reciprocal feedback loop between FOXF2 and FOXQ1 to induce cell differentiation and restore tissue homeostasis is a promising strategy for the treatment of aggressive BLBC.-Kang, L.-J., Yu, Z.-H., Cai, J., He, R., Lu, J.-T., Hou, C., Wang, Q.-S., Li, X.-Q., Zhang, R., Feng, Y.-M. Reciprocal transrepression between FOXF2 and FOXQ1 controls basal-like breast cancer aggressiveness.