دورية أكاديمية
Intracellular annexin A2 regulates NF-kappa B signaling by binding to the p50 subunit: implications for gemcitabine resistance in pancreatic cancer
| العنوان: | Intracellular annexin A2 regulates NF-kappa B signaling by binding to the p50 subunit: implications for gemcitabine resistance in pancreatic cancer |
|---|---|
| المؤلفون: | 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, Yeon-Soo, Lee, SC Lee, S. C., Park, SG Park, S. G., Bae, KH Bae, K-H |
| بيانات النشر: | NATURE PUBLISHING GROUP |
| سنة النشر: | 2015 |
| المجموعة: | Korea Advanced Institute of Science and Technology: KOASAS - KAIST Open Access Self-Archiving System |
| مصطلحات موضوعية: | DRUG-RESISTANCE, UP-REGULATION, IN-VIVO, CELLS, ACTIVATION, GROWTH, DIFFERENTIATION, PROGASTRIN, INTERLEUKIN-6, PROGRESSION |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/cddis.2014.558 |
| الإتاحة: | https://doi.org/10.1038/cddis.2014.558Test http://hdl.handle.net/10203/195562Test |
| رقم الانضمام: | edsbas.4E9F0830 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/cddis.2014.558 |
|---|