Research Paper Volume 12, Issue 14 pp 14391—14405
The cross-talk between DDR1 and STAT3 promotes the development of hepatocellular carcinoma
- 1 Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou,Guangdong Province, China
- 2 State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province,China
Received: February 24, 2020 Accepted: May 27, 2020 Published: July 27, 2020https://doi.org/10.18632/aging.103482
How to Cite
Copyright © 2020 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective: To investigate the function of discoidin domain receptor 1 (DDR1) in hepatocellular carcinoma (HCC) and to further clarify the underlying mechanism.
Results: DDR1 was significantly increased in HCC tissues and cells, which was related to clinical staging and prognosis of HCC. Upregulation of DDR1 promoted EMT and glutamine metabolism in HCC cells, while loss of DDR1 showed the opposite effects. STAT3 bound with the promoter of DDR1, and facilitated the phosphorylation of STAT3. In turn, activation of STAT3 increased the expression of DDR1. Silencing of STAT3 removed the promoting effect of DDR1 on proliferation, migration and invasion of HCC cells. The in vivo tumor growth assay showed that the cross-talk between DDR1 and STAT3 promoted HCC tumorigenesis.
Conclusions: Our research revealed the positive feedback of DDR1 and STAT3 promoted EMT and glutamine metabolism in HCC, which provided some experimental basis for clinical treatment or prevention of HCC.
Materials and methods: The mRNA expression of DDR1 was detected by qRT-PCR. CCK8 assay, wound healing assay and transwell assay were used to detect the DDR1/ STAT3 function on proliferation, migration and invasion in HCC cells. Western blot was used to calculate protein level of DDR1, STAT3, epithelial-mesenchymal transition (EMT) related proteins.