Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.
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ABSTRACT:
SUBMITTER: Laklai H
PROVIDER: S-EPMC4860133 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
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Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.
Laklai Hanane H Miroshnikova Yekaterina A YA Pickup Michael W MW Collisson Eric A EA Kim Grace E GE Barrett Alex S AS Hill Ryan C RC Lakins Johnathon N JN Schlaepfer David D DD Mouw Janna K JK LeBleu Valerie S VS Roy Nilotpal N Novitskiy Sergey V SV Johansen Julia S JS Poli Valeria V Kalluri Raghu R Iacobuzio-Donahue Christine A CA Wood Laura D LD Hebrok Matthias M Hansen Kirk K Moses Harold L HL Weaver Valerie M VM
Nature medicine 20160418 5
Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin m ...[more]
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