title: 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.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Intervention Therapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Haohao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Intervention Therapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Shao
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Lisong
authors.initials: L
authors.lastname: Teng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D061986:MCF-7 Cells; D010750:Phosphoproteins / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors