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

研究成果: Article査読

535 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)456-469
ページ数14
ジャーナルCancer Cell
19
4
DOI
出版ステータスPublished - 2011 4 12

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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