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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Zhang Y,Yan W,Collins MA,Bednar F,Rakshit S,Zetter BR,Stanger BZ,Chung I,Rhim AD,di Magliano MPdoi
10.1158/0008-5472.CAN-13-1558-Tsubject
Has Abstractpub_date
2013-10-15 00:00:00pages
6359-74issue
20eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-13-1558-Tjournal_volume
73pub_type
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