The cross-talk between DDR1 and STAT3 promotes the development of hepatocellular carcinoma.
Carcinoma, Hepatocellular
/ genetics
Cell Movement
/ genetics
Cell Proliferation
Discoidin Domain Receptor 1
/ genetics
Epithelial-Mesenchymal Transition
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Gene Silencing
Glutamine
/ metabolism
Humans
Liver Neoplasms
/ genetics
Neoplasm Invasiveness
/ genetics
Neoplasm Metastasis
/ pathology
Phosphorylation
Prognosis
Receptor Cross-Talk
STAT3 Transcription Factor
/ genetics
DDR1
EMT
STAT3
glutamine metabolism
hepatocellular carcinoma
Journal
Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617
Informations de publication
Date de publication:
27 07 2020
27 07 2020
Historique:
received:
24
02
2020
accepted:
27
05
2020
pubmed:
28
7
2020
medline:
25
3
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
To investigate the function of discoidin domain receptor 1 (DDR1) in hepatocellular carcinoma (HCC) and to further clarify the underlying mechanism. 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. 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. 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.
Identifiants
pubmed: 32716315
pii: 103482
doi: 10.18632/aging.103482
pmc: PMC7425490
doi:
Substances chimiques
STAT3 Transcription Factor
0
STAT3 protein, human
0
Glutamine
0RH81L854J
DDR1 protein, human
EC 2.7.10.1
Discoidin Domain Receptor 1
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14391-14405Références
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