Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma

被引:40
作者
Chen, Chang-Yu [1 ]
Lin, Yung-Song [2 ,3 ]
Chen, Chi-Long [4 ,5 ]
Chao, Pin-Zhir [6 ]
Chiou, Jeng-Fong [7 ,8 ,9 ]
Kuo, Chia-Chun [7 ]
Lee, Fei-Peng [10 ]
Lin, Yung-Feng [1 ]
Sung, Yu-Hsuan [1 ]
Lin, Yun-Tien [1 ]
Li, Chang-Fan [1 ]
Chen, Yin-Ju [7 ,11 ]
Chen, Chien-Ho [1 ]
机构
[1] Taipei Med Univ, Coll Med Sci & Technol, Sch Med Lab Sci & Biotechnol, Taipei, Taiwan
[2] Taipei Med Univ, Coll Med, Sch Med, Dept Otolaryngol, Taipei, Taiwan
[3] Chi Mei Med Ctr, Dept Otolaryngol, Tainan, Taiwan
[4] Taipei Med Univ Hosp, Dept Pathol, Taipei, Taiwan
[5] Taipei Med Univ, Sch Med, Coll Med, Dept Pathol, Taipei, Taiwan
[6] Shuang Ho Hosp, Dept Otolaryngol, New Taipei City, Taiwan
[7] Taipei Med Univ Hosp, Dept Radiat Oncol, Taipei, Taiwan
[8] Taipei Med Univ, Coll Med, Sch Med, Dept Radiol, Taipei, Taiwan
[9] Taipei Med Univ Hosp, Ctr Canc, Taipei, Taiwan
[10] Wan Fang Hosp, Dept Otolaryngol Head & Neck Surg, Taipei, Taiwan
[11] Taipei Med Univ, Coll Oral Med, Grad Inst Biomed Mat & Engn, Taipei, Taiwan
关键词
nasopharyngeal carcinoma (NPC); annexin A2 (ANXA2); chemotherapy; radiotherapy; epithelial-mesenchymal transition (EMT); CANCER STEM-CELLS; ACCESSORY CELLS; DENDRITIC CELLS; EXPRESSION; INVASION; MECHANISMS; AKT; PHOSPHORYLATION; ANGIOGENESIS; CHEMOTHERAPY;
D O I
10.18632/oncotarget.4521
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:26946 / 26959
页数:14
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