A Feedback loop comprising EGF/TGF-α Sustains TFCP2-mediated Breast Cancer Progression.

Stemness and epithelial-mesenchymal transition (EMT) are two fundamental characteristics of metastasis that are controlled by diverse regulatory factors, including transcription factors. Compared with other subtypes of breast cancer, basal-type or triple-negative breast cancer (TNBC) have high frequencies of tumor relapse. However, the role of alpha-globin transcription factor CP2 (TFCP2) has not been reported as an oncogenic driver in those breast cancers. Here we show that TFCP2 is a potent factor essential for EMT, stemness, and metastasis in breast cancer. TFCP2 directly bound promoters of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) to regulate their expression and stimulate autocrine signaling via epidermal growth factor receptor (EGFR). These findings indicate that TFCP2 is a new anti-metastatic target and reveal a novel regulatory mechanism in which a positive feedback loop comprising EGF/TGF-α and AKT can control malignant breast cancer progression.