Abstract

The metastasis of hepatocellular carcinoma (HCC) poses a significant threat to the survival of patients. G protein-coupled receptor 56 (GPR56) has garnered extensive attention within malignant tumor research and plays a crucial role in cellular surface signal transmission. Nonetheless, its precise function in HCC remains ambiguous. Our investigation reveals a notable rise in GPR56 expression levels in human HCC cases, with heightened GPR56 levels correlating with unfavorable prognoses. GPR56 regulates TGF-β pathway by interacting with TGFBR1, thereby promoting HCC metastasis. At the same time, GPR56 is subject to regulation by the canonical cascade of TGF-β signaling, thereby establishing a positive feedback loop. Furthermore, the combination application of TGFBR1 inhibitor galunisertib (GAL) and GPR56 inhibitor Dihydromunduletone (DHM), significantly inhibits HCC metastasis. Interventions towards this signaling pathway could offer a promising therapeutic approach to effectively impede the metastasis of GPR56-mediated HCC.

Details

Title
GPR56 facilitates hepatocellular carcinoma metastasis by promoting the TGF-β signaling pathway
Author
Luo, Yiming 1 ; Lu, Junli 1 ; Lei, Zhen 1 ; Rao, Dean 1 ; Wang, Tiantian 1 ; Fu, Chenan 1 ; Zhu, He 1 ; Zhang, Zhiwei 1 ; Liao, Zhibin 1   VIAFID ORCID Logo  ; Liang, Huifang 1   VIAFID ORCID Logo  ; Huang, Wenjie 2   VIAFID ORCID Logo 

1  Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (GRID:grid.412793.a) (ISNI:0000 0004 1799 5032) 
2  Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (GRID:grid.412793.a) (ISNI:0000 0004 1799 5032); Ministry of Education and Ministry of Public Health, Clinical Medicine Research Center for Hepatic Surgery of Hubei Province; Key Laboratory of Organ Transplantation, Wuhan, China (GRID:grid.412793.a) 
Pages
715
Publication year
2024
Publication date
Oct 2024
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-024-07095-6
ProQuest document ID
3111717642
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.