Inhibition of glycogen synthase kinase-3 activity triggers an apoptotic response in pancreatic cancer cells through JNK-dependent mechanisms
| العنوان: | Inhibition of glycogen synthase kinase-3 activity triggers an apoptotic response in pancreatic cancer cells through JNK-dependent mechanisms |
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| المؤلفون: | Marie-Josée Boucher, Sébastien Cagnol, Isabelle Tremblay, Benoit Marchand |
| المصدر: | Carcinogenesis. 33:529-537 |
| بيانات النشر: | Oxford University Press (OUP), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Cancer Research, Indoles, animal structures, Cell Survival, MAP Kinase Signaling System, Pyridines, Apoptosis, macromolecular substances, Biology, Maleimides, Glycogen Synthase Kinase 3, GSK-3, Cell Line, Tumor, Proto-Oncogene Proteins, Pancreatic cancer, medicine, Humans, RNA, Messenger, Phosphorylation, Glycogen synthase, Receptor, Pancreas, Cell Proliferation, Anthracenes, Bcl-2-Like Protein 11, Kinase, Cell growth, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, Receptors, Death Domain, General Medicine, medicine.disease, Cell biology, Pancreatic Neoplasms, Pyrimidines, Cell culture, biology.protein, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt |
| الوصف: | Recent evidences suggest that the activity of glycogen synthase kinase-3 (GSK3) contributes to the tumorigenic potential of pancreatic cancer cells through modulation of cell proliferation and survival. However, further investigations are needed to identify GSK3-dependent mechanisms involved in the control of pancreatic cancer cell proliferation and survival. This study was undertaken to provide further support for a role of GSK3 in pancreatic cancer cell growth as well as to identify new cellular and molecular mechanisms involved. Herein, we demonstrate that prolonged inhibition of GSK3 triggers an apoptotic response only in human pancreatic cancer cells but not in human non-transformed pancreatic epithelial cells. We show that prolonged inhibition of GSK3 activity increases Bim messenger RNA and protein expressions. Moreover, we provide evidence that activation of the c-jun N-terminal kinase (JNK) pathway is necessary for the GSK3 inhibition-mediated increase in Bim expression and apoptotic response. Finally, we demonstrate that concomitant inhibition of GSK3 potentiates the death ligand-induced apoptotic response in pancreatic cancer cells but not in non-transformed pancreatic epithelial cells and that this effect also requires JNK activity. Considering that different approaches leading to stimulation of death receptor signaling are under clinical trials for treatment of unresectable or metastatic pancreatic cancer, inhibition of GSK3 could represent an attractive new avenue to improve their effectiveness. |
| تدمد: | 1460-2180 0143-3334 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdface4aea213e6991cc7c2826ee0697Test https://doi.org/10.1093/carcin/bgr309Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fdface4aea213e6991cc7c2826ee0697 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602180 01433334 |
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