title: Knockdown of the T-box transcription factor Brachyury increases sensitivity of adenoid cystic carcinoma cells to chemotherapy and radiation in vitro: implications for a new therapeutic principle.
abstract: Adenoid cystic carcinoma (AdCC) is highly metastatic and resistant to chemotherapy and radiotherapy. Recently, we reported that the T-box transcription factor Brachyury is a potential regulator of cancer stem cells (CSCs). Specifically, growth of CSCs was found to be controlled by Brachyury knockdown in AdCC. Since CSCs are resistant to chemotherapy and radiotherapy, this finding provides a new principle for therapies targeting CSCs. In the present study, we established that Brachyury knockdown suppresses chemoresistance and radioresistance in vitro. Brachyury was knocked down by transfecting Brachyury short hairpin RNA (shRNA) into the AdCC CSC cell line ACCS-M GFP. Brachyury knockdown significantly inhibited cell migration and invasion and suppressed chemoresistance. A quantitative PCR array of drug transporter genes revealed that knockdown of Brachyury caused down-regulation of ATP-binding cassette transporter genes. Furthermore, ACCS-M GFP radioresistance was significantly suppressed by Brachyury knockdown. Knockdown of Brachyury significantly sensitized ACCS-M GFP cells to chemoradiotherapy. This study demonstrates that Brachyury knockdown reduces invasiveness and chemoresistance and radioresistance of CSCs in vivo. Therefore, Brachyury knockdown may be a useful therapeutic tool for sensitizing CSCs to conventional chemoradiotherapy.
authors: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Yosuke
authors: Y
authors: Kobayashi
authors: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Tsuyoshi
authors: T
authors: Sugiura
authors: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Ikumi
authors: I
authors: Imajyo
authors: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Miyuki
authors: M
authors: Shimoda
authors: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Kotaro
authors: K
authors: Ishii
authors: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Naonari
authors: N
authors: Akimoto
authors: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Naoya
authors: N
authors: Yoshihama
authors: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Yoshihide
authors: Y
authors: Mori
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D015820:Cadherins / Q000235:genetics; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D059248:Chemoradiotherapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition; D005326:Fetal Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000528:radiation effects; D034622:RNA Interference; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000235:genetics*; D058978:Reduced Folate Carrier Protein / Q000096:biosynthesis; D055748:SOXB1 Transcription Factors / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics*; D014746:Vimentin / Q000096:biosynthesis; D000098908:Brachyury Protein
chemical_list: D018528:ATP-Binding Cassette Transporters; D015820:Cadherins; D005326:Fetal Proteins; D034741:RNA, Small Interfering; D058978:Reduced Folate Carrier Protein; D055748:SOXB1 Transcription Factors; D020825:T-Box Domain Proteins; D014746:Vimentin; D000098908:Brachyury Protein; C548699:SLC19A1 protein, human; C527782:SOX2 protein, human