title: Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma.
abstract: The expression of annexin A2 (ANXA2) in nasopharyngeal carcinoma (NPC) cells induces the immunosuppressive response in dendritic cells; however, the oncogenic effect and clinical significance of ANXA2 have not been fully investigated in NPC cells. Immunohistochemical staining for ANXA2 was performed in 61 patients and the association with clinicopathological status was determined. Short hairpin (sh)RNA knockdown of ANXA2 was used to examine cellular effects of ANXA2, by investigating alterations in cell proliferation, migration, invasion, adhesion, tube-formation assay, and chemo- and radiosensitivity assays were performed. RT-qPCR, Western blotting, and immunofluorescence were applied to determine molecular expression levels. Clinical association studies showed that the expression of ANXA2 was significantly correlated with metastasis (p = 0.0326) and poor survival (p = 0.0256). Silencing of ANXA2 suppressed the abilities of cell proliferation, adhesion, migration, invasion, and vascular formation in NPC cell. ANXA2 up-regulated epithelial-mesenchymal transition associated signal proteins. Moreover, ANXA2 reduced sensitivities to irradiation and chemotherapeutic drugs. These results define ANXA2 as a novel prognostic factor for malignant processes, and it can serve as a molecular target of therapeutic interventions for NPC.
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Otolaryngology, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Yung-Song
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Pathology, Taipei Medical University Hospital; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Shuang Ho Hospital, New Taipei City, Taiwan.
authors.forename: Pin-Zhir
authors.initials: PZ
authors.lastname: Chao
authors.affiliation: Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.|Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Jeng-Fong
authors.initials: JF
authors.lastname: Chiou
authors.affiliation: Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Wan-Fang Hospital, Taipei, Taiwan.
authors.forename: Fei-Peng
authors.initials: FP
authors.lastname: Lee
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Sung
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yun-Tien
authors.initials: YT
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chang-Fan
authors.initials: CF
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.|Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yin-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chien-Ho
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D002277:Carcinoma; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering
keywords: annexin A2 (ANXA2); chemotherapy; epithelial-mesenchymal transition (EMT); nasopharyngeal carcinoma (NPC); radiotherapy