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Published on: October 27, 2020
GPR56 facilitates hepatocellular carcinoma metastasis by promoting the TGF-β signaling pathway
Yiming Luo1, Junli Lu1, Zhen Lei1
1Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, 430030, China.
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.
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