@article{6c109c11a628444ba968d8e2e592e185,
title = "Stat3/Socs3 Activation by IL-6 Transsignaling Promotes Progression of Pancreatic Intraepithelial Neoplasia and Development of Pancreatic Cancer",
abstract = "Physiological levels of KrasG12D are sufficient to induce pancreatic intraepithelial neoplasias (PanINs); the mechanisms that drive PanIN progression are unknown. Here, we establish that, in addition to oncogenic KrasG12D, IL-6 transsignaling-dependent activation of Stat3/Socs3 is required to promote PanIN progression and pancreatic ductal adenocarcinoma (PDAC). Myeloid compartment induces Stat3 activation by secreting IL-6; consequently, IL-6 transsignaling activates Stat3 in the pancreas. Using genetic tools, we show that inactivation of IL-6 transsignaling or Stat3 inhibits PanIN progression and reduces the development of PDAC. Aberrant activation of Stat3 through homozygous deletion of Socs3 in the pancreas accelerates PanIN progression and PDAC development. Our data describe the involvement of IL-6 transsignaling/Stat3/Socs3 in PanIN progression and PDAC development.",
author = "Marina Lesina and Kurkowski, {Magdalena U.} and Katharina Ludes and Stefan Rose-John and Matthias Treiber and G{\"u}nter Kl{\"o}ppel and Akihiko Yoshimura and Wolfgang Reindl and Bence Sipos and Shizuo Akira and Schmid, {Roland M.} and Hana Alg{\"u}l",
note = "Funding Information: We thank Karen Dlubatz for excellent technical assistance. M.U.K. is an MD/PhD candidate at the Technische Universit{\"a}t M{\"u}nchen. Y.A. received grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation. S.R.-J. was supported by the Deutsche Forschungsgemeinschaft (SFB 877, TP A 1) and by the Cluster of Excellence “Inflammation at Interfaces.” H.A. and R.M.S. were supported by the Deutsche Forschungsgemeinschaft (SFB 576, TP A 10 to H.A. and R.M.S), Deutsche Krebshilfe (Grant 10994 to H.A.), Else-Kr{\"o}ner-Fresenius-Stiftung (Grant 2010_A144 to H.A.), and by promotional programs of the Technische Universit{\"a}t M{\"u}nchen (KKF-C to H.A. and KKF-A to R.M.S). S.R.-J. is inventor on patents describing the function of sgp130Fc and is a shareholder of the CONARIS Research Institute (Kiel, Germany). ",
year = "2011",
month = apr,
day = "12",
doi = "10.1016/j.ccr.2011.03.009",
language = "English",
volume = "19",
pages = "456--469",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}