2. Academic Validation
  3. WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer

WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer

  • Cancer Lett. 2019 Jun 1;451:48-57. doi: 10.1016/j.canlet.2019.02.043.
Bing-Qi Li 1,  Zhi-Yong Liang 2,  Samuel Seery 3,  Qiao-Fei Liu 4,  Lei You 5,  Tai-Ping Zhang 6,  Jun-Chao Guo 7,  Yu-Pei Zhao 8
Affiliations

Affiliations

  • 1 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: lbqi123456@sina.com.
  • 2 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: liangzhiyong1220@yahoo.com.
  • 3 School of Humanities and Social Sciences, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: sam.seery@yahoo.com.
  • 4 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: qfliu@aliyun.com.
  • 5 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: florayo@163.com.
  • 6 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: tpingzhang@yahoo.com.
  • 7 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: gjcpumch@163.com.
  • 8 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: zhao8028@263.net.
PMID: 30851419 DOI: 10.1016/j.canlet.2019.02.043
Abstract

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.

Keywords

Chemo-sensitivity; Fak; Migration/invasion; PC; WTAP.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z