Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma

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*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

43 Scopus citations

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.

Original languageEnglish
Pages (from-to)26946-26959
Number of pages14
JournalOncotarget
Volume6
Issue number29
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Annexin A2 (ANXA2)
  • Chemotherapy
  • Epithelial-mesenchymal transition (EMT)
  • Nasopharyngeal carcinoma (NPC)
  • Radiotherapy

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