Zhang, Yaqing and Yan, Wei and Collins, Meredith A. and Bednar, Filip and Rakshit, Sabita and Zetter, Bruce R. and Stanger, Ben Z. and Chung, Ivy and Rhim, Andrew D. and di Magliano, Marina Pasca (2013) Interleukin-6 Is Required for Pancreatic Cancer Progression by Promoting MAPK Signaling Activation and Oxidative Stress Resistance. Cancer Research, 73 (20). pp. 6359-6374. ISSN 0008-5472, DOI https://doi.org/10.1158/0008-5472.CAN-13-1558-T.
Full text not available from this repository.Abstract
Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multiple cell types within the tumor microenvironment. Here, we show that IL-6 is required for the maintenance and progression of pancreatic cancer precursor lesions. In fact, the lack of IL-6 completely ablates cancer progression even in presence of oncogenic Kras. Mechanistically, we show that IL-6 synergizes with oncogenic Kras to activate the reactive oxygen species detoxification program downstream of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade. In addition, IL-6 regulates the inflammatory microenvironment of pancreatic cancer throughout its progression, providing several signals that are essential for carcinogenesis. Thus, IL-6 emerges as a key player at all stages of pancreatic carcinogenesis and a potential therapeutic target. © 2013 AACR.
| Item Type: | Article |
|---|---|
| Funders: | National Institutes of Health: T32 GM07315 |
| Uncontrolled Keywords: | Animals; Disease Progression; Humans; Interleukin-6; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinases; Oxidative Stress; Pancreatic Neoplasms; Random Allocation |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 20 Nov 2019 02:34 |
| Last Modified: | 20 Nov 2019 02:34 |
| URI: | http://eprints.um.edu.my/id/eprint/23073 |
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