Intracellular annexin A2 regulates NF-kappa B signaling by binding to the p50 subunit: implications for gemcitabine resistance in pancreatic canceropen access
- Authors
- Jung, H[Jung, H.]; Kim, JS[Kim, J. S.]; Kim, WK[Kim, W. K.]; Oh, KJ[Oh, K-J]; Kim, JM[Kim, J-M]; Lee, HJ[Lee, H. J.]; Han, BS[Han, B. S.]; Kim, DS[Kim, D. S.]; Seo, YS[Seo, Y. S.]; Lee, SC[Lee, S. C.]; Park, SG[Park, S. G.]; Bae, KH[Bae, K-H]
- Issue Date
- Jan-2015
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- CELL DEATH & DISEASE, v.6
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL DEATH & DISEASE
- Volume
- 6
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/44936
- DOI
- 10.1038/cddis.2014.558
- ISSN
- 2041-4889
- Abstract
- Annexin A2 (ANXA2) expression is highly upregulated in many types of cancer. Although cell surface localization of ANXA2 has been reported to have a critical role in the progression and metastasis of a variety of tumors, including pancreatic cancer, the biological role of intracellular ANXA2 is not fully understood. Herein the role of intracellular ANXA2 was investigated in a pancreatic cancer cell line. We first determined whether ANXA2 is involved in NF-kappa B signaling pathways. ANXA2 bound to the p50 subunit of NF-kappa B in a calcium-independent manner, and the ANXA2-p50 complex translocated into the nucleus. Furthermore, ANXA2 increased the transcriptional activity of NF-kappa B in both the resting and activated states and upregulated the transcription of several target genes downstream of NF-kappa B, including that encoding interleukin (IL)-6, which contributes to anti-apoptotic signaling. In Mia-Paca2 cells, we determined the effects of wild-type ANXA2 and an ANXA2 mutant, Y23A, which suppresses the cell surface localization, on upregulation of NF-kappa B transcriptional activity and secretion of IL-6. Both wild-type and Y23A ANXA2 induced anti-apoptotic effects in response to treatment with tumor necrosis factor-alpha or gemcitabine. Based on these results, we suggest that ANXA2 mediates resistance to gemcitabine by directly increasing the activity of NF-kappa B. Collectively, these data may provide additional information about the biological role of ANXA2 in pancreatic cancer and suggest that ANXA2 is a potential biomarker for the drug resistance phenotype and a candidate therapeutic target for the treatment of pancreatic cancer.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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