作者
Hanane Laklai, Yekaterina A Miroshnikova, Michael W Pickup, Eric A Collisson, Grace E Kim, Alex S Barrett, Ryan C Hill, Johnathon N Lakins, David D Schlaepfer, Janna K Mouw, Valerie S LeBleu, Nilotpal Roy, Sergey V Novitskiy, Julia S Johansen, Valeria Poli, Raghu Kalluri, Christine A Iacobuzio-Donahue, Laura D Wood, Matthias Hebrok, Kirk Hansen, Harold L Moses, Valerie M Weaver
发表日期
2016/4/18
期刊
Nature Medicine
出版商
Nature Publishing Group
简介
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 mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were associated with …
学术搜索中的文章
H Laklai, YA Miroshnikova, MW Pickup, EA Collisson… - Nature medicine, 2016