HB‐EGF orchestrates the complex signals involved in triple‐negative and trastuzumab‐resistant breast cancer |
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Authors: | Fusanori Yotsumoto Eiji Oki Eriko Tokunaga Yoshihiko Maehara Masahide Kuroki Shingo Miyamoto |
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Institution: | 1. Department of Biochemistry, School of Medicine, Fukuoka University, Jonan‐ku, Fukuoka, Japan;2. Center for Advanced Molecular Medicine, Fukuoka University, Jonan‐ku, Fukuoka, Japan;3. Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Higashi‐ku, Fukuoka, Japan;4. Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Jonan‐ku, Fukuoka, JapanTel.: +81‐92‐801‐1011, Fax: +81‐92‐865‐4114 |
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Abstract: | A number of therapeutic strategies targeting epidermal growth factor receptor (EGFR) have not always led to success in the present state of breast cancer therapy. Notably, there is currently no way to treat trastuzumab‐resistant and triple‐negative breast cancer (TNBC). Here, we found that heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF), a member of the EGFR ligands, was predominantly expressed in breast cancer and that treatment with crossreacting material 197 (CRM197), a specific inhibitor of HB‐EGF, blocked ERK as well as AKT activation via complexes of EGFR and unknown growth factor receptors in TNBC or through complexes of EGFR and human epidermal growth factor receptor‐2 in trastuzumab‐resistant breast cancer, caused significant cell apoptosis and inhibited tumor growth. Accordingly, we can provide a novel concept that a certain EGFR ligand is recognized as a rational target against breast cancer. In addition, it is plausible that CRM197 could be an effective anticancer agent for molecularly targeted therapies. |
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Keywords: | HB‐EGF CRM197 breast cancer AKT triple‐negative breast cancer |
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