Knockdown of TAZ modifies triple-negative breast cancer cell sensitivity to EGFR inhibitors by regulating YAP expression

Abstract

Triple-negative breast cancer (TNBC) constitutes ~10-15% of breast cancer patients and represents an aggressive subtype with poor overall prognosis. TNBC is an important clinical challenge because it does not respond well to endocrine therapy and have a higher rate of early recurrence and distant metastasis following chemotherapy. Although it has been reported that the epidermal growth factor receptor (EGFR) was overexpressed in ~80% of TNBC, anti-EGFR therapy showed limited clinical benefit according to phase II studies. In this study, we first observed that knockdown of the transcriptional coactivator with PDZ-binding domain (TAZ) gene can regulate the sensitivity of TNBC cell lines to EGFR inhibitors (EGFRI) in a cell context-depended manner. Furthermore, in certain breast cancer cell lines the YES-associated protein, paralog of TAZ (YAP) expression can be upregulated by TAZ inhibition which leads to EGFRI resistance. These results suggest a specific inhibitor to TAZ/YAP combined with anti-EGFR therapy may prove effective and provide a reason why targeting EGFR showed limited clinical benefit in TNBC treatment.