title: cIAP2 promotes gallbladder cancer invasion and lymphangiogenesis by activating the NF-κB pathway.
abstract: Several studies have produced contradictory findings about the prognostic implications for inhibitor of apoptosis proteins (IAP) in different types of cancer. Cellular inhibitor of apoptosis 2 (cIAP2/BIRC) is one of the most extensively characterized human IAP. To date, no studies have focused on the expression level of cIAP2 in human gallbladder cancer (GBC), and the mechanism of cIAP2 in GBC invasion and lymphangiogenesis remains unclear. Therefore, in the present study, cIAP2 expression in GBC was detected using quantitative real-time polymerase chain reaction and immunohistochemistry, and the relationship between cIAP2 levels in cancer tissues and the clinicopathological characteristics of patients was analyzed. The biological effect of cIAP2 in GBC cells was tested using the Cell Counting Kit-8 Assay, Transwell assays and the ability of human dermal lymphatic endothelial cells (HDLEC) to undergo tube formation. The role of cIAP2 in activating the NF-κB pathway was determined using a dual-luciferase reporter assay, immunofluorescence staining, western blotting and ELISA. Finally, an animal model was used to further confirm the role of cIAP2 in lymphangiogenesis. We showed that cIAP2 expression was elevated in human GBC tissues and correlated with a negative prognosis for patients. Moreover, cIAP2 was identified as a lymphangiogenic factor of GBC cells and, thus, promoted lymph node metastasis in GBC cells. Our study is the first to suggest that cIAP2 can promote GBC invasion and lymphangiogenesis by activating the NF-κB pathway.
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumour Microbiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumour Microbiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Chengzong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumour Microbiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Haijie
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumour Microbiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Nanhong
authors.initials: N
authors.lastname: Tang
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Xiujin
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumour Microbiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: She
authors.affiliation: Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumour Microbiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Yanling
authors.identifier: http://orcid.org/0000-0002-6975-915X
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000368:Aged; D000818:Animals; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D042583:Lymphangiogenesis / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics*; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases
keywords: Cellular inhibitor of apoptosis 2; gallbladder cancer; invasion; lymphangiogenesis; nuclear factor-κB