Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma
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Chang-Yu Chen1,*, Yung-Song Lin2,3,*, Chi-Long Chen4,*, Pin-Zhir Chao5, Jeng-Fong Chiou6,7,8, Chia-Chun Kuo6, Fei-Peng Lee9, Yung-Feng Lin1, Yu-Hsuan Sung1, Yun-Tien Lin1, Chang-Fan Li1, Yin-Ju Chen6,10,*, Chien-Ho Chen1,*
1School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
2Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3Department of Otolaryngology, Chi Mei Medical Center, Tainan, Taiwan
4Department of Pathology, Taipei Medical University Hospital; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
5Department of Otolaryngology, Shuang Ho Hospital, New Taipei City, Taiwan
6Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan
7Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
8Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan
9Department of Otolaryngology, Head and Neck Surgery, Wan-Fang Hospital, Taipei, Taiwan
10Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
*These authors have contributed equally to this work
Chien-Ho Chen, e-mail: firstname.lastname@example.org
Yin-Ju Chen, e-mail: email@example.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
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.
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