Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma

// Chang-Yu Chen 1, * , Yung-Song Lin 2, 3, * , Chi-Long Chen 4, * , Pin-Zhir Chao 5 , Jeng-Fong Chiou 6, 7, 8 , Chia-Chun Kuo 6 , Fei-Peng Lee 9 , Yung-Feng Lin 1 , Yu-Hsuan Sung 1 , Yun-Tien Lin 1 , Chang-Fan Li 1 , Yin-Ju Chen 6, 10, * , Chien-Ho Chen 1, * 1 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 2 Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 3 Department of Otolaryngology, Chi Mei Medical Center, Tainan, Taiwan 4 Department of Pathology, Taipei Medical University Hospital; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 5 Department of Otolaryngology, Shuang Ho Hospital, New Taipei City, Taiwan 6 Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan 7 Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 8 Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan 9 Department of Otolaryngology, Head and Neck Surgery, Wan-Fang Hospital, Taipei, Taiwan 10 Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Chien-Ho Chen, e-mail: chenchho@tmu.edu.tw Yin-Ju Chen, e-mail: yjchen1113@gmail.com Keywords: nasopharyngeal carcinoma (NPC), annexin A2 (ANXA2), chemotherapy, radiotherapy, epithelial-mesenchymal transition (EMT) Received: January 29, 2015      Accepted: June 26, 2015      Published: July 09, 2015 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.