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

IF 8.1 1区生物学 Q1 CELL BIOLOGY

Cell Death & Disease Pub Date : 2024-10-01 DOI:10.1038/s41419-024-07095-6

Yiming Luo, Junli Lu, Zhen Lei, Dean Rao, Tiantian Wang, Chenan Fu, He Zhu, Zhiwei Zhang, Zhibin Liao, Huifang Liang, Wenjie Huang

{"title":"GPR56 facilitates hepatocellular carcinoma metastasis by promoting the TGF-β signaling pathway.","authors":"Yiming Luo, Junli Lu, Zhen Lei, Dean Rao, Tiantian Wang, Chenan Fu, He Zhu, Zhiwei Zhang, Zhibin Liao, Huifang Liang, Wenjie Huang","doi":"10.1038/s41419-024-07095-6","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445230/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death & Disease","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41419-024-07095-6","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

GPR56 通过促进 TGF-β 信号通路促进肝细胞癌转移。

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，并在细胞表面信号传递中发挥着关键作用。然而，它在 HCC 中的确切功能仍不明确。我们的研究发现，在人类 HCC 病例中，GPR56 的表达水平明显升高，GPR56 水平的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 还受 TGF-β 信号的典型级联调控，从而建立了一个正反馈回路。此外，TGFBR1 抑制剂 galunisertib（GAL）和 GPR56 抑制剂 Dihydromunduletone（DHM）联合应用可显著抑制 HCC 转移。对这一信号通路的干预可为有效阻止 GPR56 介导的 HCC 转移提供一种有前景的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Death & Disease CELL BIOLOGY-

CiteScore

15.10

自引率

2.20%

发文量

935

审稿时长

2 months

期刊介绍： Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism