期刊
CANCER LETTERS
卷 451, 期 -, 页码 48-57出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.02.043
关键词
WTAP; Fak; PC; Migration/invasion; Chemo-sensitivity
类别
资金
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-3-019]
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT32014]
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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