title: Annexin A4-nuclear factor-κB feedback circuit regulates cell malignant behavior and tumor growth in gallbladder cancer.
abstract: Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system. However, the mechanisms underlying its tumor initiation, progression, and metastasis are not yet fully understood. The annexin A4 (ANXA4) gene is highly expressed in GBC tissues and may play an important role in the initiation and progression of this disease. In this study, we examined the up-regulation of ANXA4 in human GBC tissues and cell lines. Elevated ANXA4 correlated well with invasion depth in GBC patients and predicted a poor prognosis. In vitro, GBC-SD and NOZ cells with ANXA4 knockdown demonstrated increased apoptosis and inhibited cell growth, migration, and invasion. Interactions between ANXA4 and nuclear factor-κB (NF-κB) p65 proteins were detected. In vivo, ANXA4 knockdown inhibited tumor growth of GBC cells in nude mice and down-regulated the expression of downstream factors in the NF-κB signaling pathway. Taken together, these data indicate that up-regulation of ANXA4 leads to activation of the NF-κB pathway and its target genes in a feedback regulatory mechanism via the p65 subunit, resulting in tumor growth in GBC.
authors: Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors: Hou-Shan
authors: HS
authors: Yao
authors: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China.
authors: Chang
authors: C
authors: Sun
authors: Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors: Xin-Xing
authors: XX
authors: Li
authors: Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors: Yi
authors: Y
authors: Wang
authors: Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors: Kai-Zhou
authors: KZ
authors: Jin
authors: Institute of Intervention Vessel, Tongji University, North Zhongshan Road, Shanghai 200070, China.|Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors: Xiao-Ping
authors: XP
authors: Zhang
authors: Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors: Zhi-Qian
authors: ZQ
authors: Hu
mesh_terms: D000818:Animals; D017314:Annexin A4 / Q000378:metabolism*; D045744:Cell Line, Tumor; D005706:Gallbladder Neoplasms / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D008819:Mice, Nude; D011485:Protein Binding; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D017314:Annexin A4; C498143:RELA protein, human; D051996:Transcription Factor RelA