Stat3/Socs3 Activation by IL-6 Transsignaling Promotes Progression of Pancreatic Intraepithelial Neoplasia and Development of Pancreatic Cancer

Marina Lesina, Magdalena U. Kurkowski, Katharina Ludes, Stefan Rose-John, Matthias Treiber, Günter Klöppel, Akihiko Yoshimura, Wolfgang Reindl, Bence Sipos, Shizuo Akira, Roland M. Schmid, Hana Algül

Research output: Contribution to journalArticle

506 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)456-469
Number of pages14
JournalCancer Cell
Volume19
Issue number4
DOIs
Publication statusPublished - 2011 Apr 12

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Lesina, M., Kurkowski, M. U., Ludes, K., Rose-John, S., Treiber, M., Klöppel, G., Yoshimura, A., Reindl, W., Sipos, B., Akira, S., Schmid, R. M., & Algül, H. (2011). Stat3/Socs3 Activation by IL-6 Transsignaling Promotes Progression of Pancreatic Intraepithelial Neoplasia and Development of Pancreatic Cancer. Cancer Cell, 19(4), 456-469. https://doi.org/10.1016/j.ccr.2011.03.009