PMID- 32716315
OWN - NLM
STAT- MEDLINE
DCOM- 20210324
LR  - 20210324
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 12
IP  - 14
DP  - 2020 Jul 27
TI  - The cross-talk between DDR1 and STAT3 promotes the development of hepatocellular 
      carcinoma.
PG  - 14391-14405
LID - 10.18632/aging.103482 [doi]
AB  - 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.
FAU - Lin, Ye
AU  - Lin Y
AD  - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou,Guangdong Province, China.
FAU - Jin, Haosheng
AU  - Jin H
AD  - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou,Guangdong Province, China.
FAU - Wu, Xianqiu
AU  - Wu X
AD  - 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.
FAU - Jian, Zhixiang
AU  - Jian Z
AD  - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou,Guangdong Province, China.
FAU - Zou, Xiongfeng
AU  - Zou X
AD  - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou,Guangdong Province, China.
FAU - Huang, Jianfeng
AU  - Huang J
AD  - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou,Guangdong Province, China.
FAU - Guan, Renguo
AU  - Guan R
AD  - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou,Guangdong Province, China.
FAU - Wei, Xiangling
AU  - Wei X
AD  - Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou,Guangdong Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200727
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0RH81L854J (Glutamine)
RN  - EC 2.7.10.1 (DDR1 protein, human)
RN  - EC 2.7.10.1 (Discoidin Domain Receptor 1)
SB  - IM
MH  - Carcinoma, Hepatocellular/*genetics
MH  - Cell Movement/genetics
MH  - Cell Proliferation
MH  - Discoidin Domain Receptor 1/*genetics
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Gene Silencing
MH  - Glutamine/metabolism
MH  - Humans
MH  - Liver Neoplasms/*genetics
MH  - Neoplasm Invasiveness/genetics
MH  - Neoplasm Metastasis/pathology
MH  - Phosphorylation
MH  - Prognosis
MH  - Receptor Cross-Talk
MH  - STAT3 Transcription Factor/*genetics
PMC - PMC7425490
OTO - NOTNLM
OT  - DDR1
OT  - EMT
OT  - STAT3
OT  - glutamine metabolism
OT  - hepatocellular carcinoma
COIS- CONFLICTS OF INTEREST: The authors declare they have no conflicts interest.
EDAT- 2020/07/28 06:00
MHDA- 2021/03/25 06:00
PMCR- 2020/07/31
CRDT- 2020/07/28 06:00
PHST- 2020/02/24 00:00 [received]
PHST- 2020/05/27 00:00 [accepted]
PHST- 2020/07/28 06:00 [pubmed]
PHST- 2021/03/25 06:00 [medline]
PHST- 2020/07/28 06:00 [entrez]
PHST- 2020/07/31 00:00 [pmc-release]
AID - 103482 [pii]
AID - 10.18632/aging.103482 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2020 Jul 27;12(14):14391-14405. doi: 10.18632/aging.103482. 
      Epub 2020 Jul 27.