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GPR56 通过促进 TGF-β 信号通路促进肝细胞癌转移。

GPR56 facilitates hepatocellular carcinoma metastasis by promoting the TGF-β signaling pathway.

机构信息

Hepatic 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.

Clinical Medicine Research Center for Hepatic Surgery of Hubei Province; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, Hubei, 430030, China.

出版信息

Cell Death Dis. 2024 Oct 1;15(10):715. doi: 10.1038/s41419-024-07095-6.

DOI:10.1038/s41419-024-07095-6
PMID:39353900
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11445230/
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.

摘要

肝细胞癌 (HCC) 的转移对患者的生存构成重大威胁。G 蛋白偶联受体 56 (GPR56) 在恶性肿瘤研究中受到广泛关注，在细胞表面信号转导中发挥着关键作用。然而，其在 HCC 中的确切功能仍不清楚。我们的研究表明，GPR56 在人 HCC 病例中的表达水平显著升高，GPR56 水平升高与预后不良相关。GPR56 通过与 TGFBR1 相互作用调节 TGF-β 通路，从而促进 HCC 转移。同时，GPR56 受到 TGF-β 信号转导的经典级联调节，从而建立正反馈环。此外，TGFBR1 抑制剂 galunisertib (GAL) 和 GPR56 抑制剂 Dihydromunduletone (DHM) 的联合应用显著抑制 HCC 转移。针对该信号通路的干预可能提供一种有前途的治疗方法，有效抑制 GPR56 介导的 HCC 转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/a1641b55af38/41419_2024_7095_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/a7d190f6b95e/41419_2024_7095_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/d153302da474/41419_2024_7095_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/6852518c2d24/41419_2024_7095_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/3f7ebf115ab6/41419_2024_7095_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/681c82bea4a4/41419_2024_7095_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/a1641b55af38/41419_2024_7095_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/a7d190f6b95e/41419_2024_7095_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/d153302da474/41419_2024_7095_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/8d5a5f4288cf/41419_2024_7095_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/6852518c2d24/41419_2024_7095_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/3f7ebf115ab6/41419_2024_7095_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/681c82bea4a4/41419_2024_7095_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e1/11445230/a1641b55af38/41419_2024_7095_Fig7_HTML.jpg

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