Intracellular annexin A2 regulates NF-κB signaling by binding to the p50 subunit: implications for gemcitabine resistance in pancreatic cancer

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Title
Intracellular annexin A2 regulates NF-κB signaling by binding to the p50 subunit: implications for gemcitabine resistance in pancreatic cancer
Author(s)
Hyeyoon Jung; Jang Seong Kim; Won Kon KimKyoung Jin Oh; J M Kim; H J Lee; Baek Soo Han; D S Kim; Y S Seo; Sang Chul LeeSung Goo ParkKwang-Hee Bae
Bibliographic Citation
Cell Death & Disease, vol. 6, no. 1, pp. e1606-e1606
Publication Year
2015
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-κB signaling pathways. ANXA2 bound to the p50 subunit of NF-κB in a calcium-independent manner, and the ANXA2-p50 complex translocated into the nucleus. Furthermore, ANXA2 increased the transcriptional activity of NF-κB in both the resting and activated states and upregulated the transcription of several target genes downstream of NF-κB, 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-κB 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-α or gemcitabine. Based on these results, we suggest that ANXA2 mediates resistance to gemcitabine by directly increasing the activity of NF-κB. 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.
ISSN
2041-4889
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/cddis.2014.558
Type
Article
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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