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: Chang-Yu Chen, Yung-Song Lin, Chi-Long Chen, Pin-Zhir Chao, Jeng-Fong Chiou, Chia-Chun Kuo, Fei-Peng Lee, Yung-Feng Lin, Yu-Hsuan Sung, Yun-Tien Lin, Chang-Fan Li, Yin-Ju Chen, Chien-Ho Chen
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 29 Pg. 26946-59 (Sep 29 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26196246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ANXA2 protein, human
• Annexin A2
• Antineoplastic Agents
• RNA, Small Interfering

Topics

• Adult
• Aged
• Aged, 80 and over
• Annexin A2 (antagonists & inhibitors, metabolism)
• Antineoplastic Agents (chemistry, therapeutic use)
• Carcinoma
• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Cell Transformation, Neoplastic (genetics)
• Drug Resistance, Neoplasm
• Epithelial-Mesenchymal Transition
• Female
• Gene Silencing
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (drug therapy, metabolism)
• Phenotype
• Prognosis
• RNA, Small Interfering (genetics)
• Signal Transduction