作者
Hong Jiang, Xiuting Liu, Brett L Knolhoff, Samarth Hegde, Kyung Bae Lee, Hongmei Jiang, Ryan C Fields, Jonathan A Pachter, Kian-Huat Lim, David G DeNardo
发表日期
2020/1/1
期刊
Gut
卷号
69
期号
1
页码范围
122-132
出版商
BMJ Publishing Group
简介
Objective
We investigated how pancreatic cancer developed resistance to focal adhesion kinase (FAK) inhibition over time.
Design
Pancreatic ductal adenocarcinoma (PDAC) tumours from KPC mice (p48-CRE; LSL-KRasG12D/wt; p53flox/wt) treated with FAK inhibitor were analysed for the activation of a compensatory survival pathway in resistant tumours. We identified pathways involved in the regulation of signal transducer and activator of transcription 3 (STAT3) signalling on FAK inhibition by gene set enrichment analysis and verified these outcomes by RNA interference studies. We also tested combinatorial approaches targeting FAK and STAT3 in syngeneic transplantable mouse models of PDAC and KPC mice.
Results
In KPC mice, the expression levels of phosphorylated STAT3 (pSTAT3) were increased in PDAC cells as they progressed on FAK inhibitor therapy. This progression corresponded to decreased …
学术搜索中的文章
H Jiang, X Liu, BL Knolhoff, S Hegde, KB Lee, H Jiang… - Gut, 2020