A Feedback Loop Comprising EGF/TGFα Sustains TFCP2-Mediated Breast Cancer Progression

Yi Zhao, Neha Kaushik, Jae Hyeok Kang, Nagendra Kumar Kaushik, Seung Han Son, Nizam Uddin, Min Jung Kim, Chul Geun Kim, Su Jae Lee

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1 Scopus citations

Abstract

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) has 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 EGF and TGFα to regulate their expression and stimulate autocrine signaling via EGFR. These findings indicate that TFCP2 is a new antimetastatic target and reveal a novel regulatory mechanism in which a positive feedback loop comprising EGF/TGFα and AKT can control malignant breast cancer progression. SIGNIFICANCE: TFCP2 is a new antimetastatic target that controls TNBC progression via a positive feedback loop between EGF/TGFα and the AKT signaling axis.

Original languageEnglish
Pages (from-to)2217-2229
Number of pages13
JournalCancer Research
Volume80
Issue number11
DOIs
StatePublished - 2020 Jun 1

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    Zhao, Y., Kaushik, N., Kang, J. H., Kaushik, N. K., Son, S. H., Uddin, N., Kim, M. J., Kim, C. G., & Lee, S. J. (2020). A Feedback Loop Comprising EGF/TGFα Sustains TFCP2-Mediated Breast Cancer Progression. Cancer Research, 80(11), 2217-2229. https://doi.org/10.1158/0008-5472.CAN-19-2908