title: TAZ regulates cell proliferation and sensitivity to vitamin D3 in intrahepatic cholangiocarcinoma.
abstract: The transcriptional coactivator with PDZ binding motif (TAZ) is reported as one of the nuclear effectors of Hippo-related pathways. TAZ is found overexpressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in Intrahepatic Cholangiocarcinoma (ICC). In this study, we found that TAZ is expressed more in ICC tissues than in peritumoral tissue, and a robust expression of TAZ is correlated with a lower overall survival rate of ICC patients after hepatectomy. TAZ knockdown results in an increase in cell apoptosis, a promotion of cell-cycle arrest and a decrease in tumor size and weight in vivo through an increased expression of p53. Vitamin D3 can also inhibit cell proliferation by promoting p53 expression in ICC cells. A reduction in TAZ can also enhance the sensitivity of tumor cells to vitamin D by regulating the p53/CYP24A1 pathway. In conclusion, TAZ is associated with the proliferation and drug-resistance of ICC cells, and could be a novel therapeutic target for the treatment of ICC.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
authors.forename: Rongliang
authors.initials: R
authors.lastname: Tong
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
authors.forename: Beng
authors.initials: B
authors.lastname: Yang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Chengli
authors.initials: C
authors.lastname: Du
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Peng
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Ding
authors.affiliation: The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
authors.forename: Shaobing
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. Electronic address: drwujian@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China. Electronic address: shusenzheng@zju.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002762:Cholecalciferol / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008817:Mice, Mutant Strains; D008875:Middle Aged; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; C495901:TP53 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D016159:Tumor Suppressor Protein p53; C551991:WWTR1 protein, human; D002762:Cholecalciferol; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase
keywords: Cytochrome P450 family 24 subfamily A polypeptide 1 (CYP24A1); Intrahepatic cholangiocarcinoma (ICC); P53; Transcriptional coactivator with PDZ binding motif (TAZ); Vitamin D3