吉西他滨
胰腺癌
癌症研究
原癌基因酪氨酸蛋白激酶Src
转移
PI3K/AKT/mTOR通路
癌症
蛋白激酶B
信使核糖核酸
信号转导
生物
医学
内科学
细胞生物学
基因
生物化学
作者
Bingqi Li,Zhiyong Liang,Samuel Seery,Qiaofei Liu,Lei You,Taiping Zhang,Junchao Guo,Yupei Zhao
标识
DOI:10.1016/j.canlet.2019.02.043
摘要
WT1 associated protein (WTAP), playing an important role in several malignancies owing to its complex function in transcriptional and post-transcriptional regulation, is an independent prognostic indicator for pancreatic cancer (PC). However, its specific role and underlying mechanism in PC remain unclear. In the present study, we found that WTAP could promote migration/invasion and suppress chemo-sensitivity to gemcitabine in PC. Further mechanical investigation revealed that WTAP could bind to and stabilize Fak mRNA which in turn activated the Fak-PI3K-AKT and Fak-Src-GRB2-Erk1/2 signaling pathways. In addition, GSK2256098, a specific Fak inhibitor, could reverse WTAP-mediated chemo-resistance to gemcitabine and metastasis in PC. Taken together, Fak inhibitor might be a promising therapeutic option for PC patients with WTAP overexpression.
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