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

被引：1

作者：

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
]}

Liang, Huifang ^{[1
]}

Huang, Wenjie ^{[1
,2
,3
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr,Hubei Key Lab Hepatopancreato Bilia, Wuhan 430030, Hubei, Peoples R China

[2] Minist Educ, Clin Med Res Ctr Hepat Surg Hubei Prov, Key Lab Organ Transplantat, Wuhan 430030, Hubei, Peoples R China

[3] Minist Publ Hlth, Wuhan 430030, Hubei, Peoples R China

来源：

CELL DEATH & DISEASE | 2024年 / 15卷 / 10期

基金：

中国国家自然科学基金;

关键词：

GPR56/ADGRG1; GPCR; EXPRESSION; GROWTH; HEALTH;

D O I：

10.1038/s41419-024-07095-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-beta pathway by interacting with TGFBR1, thereby promoting HCC metastasis. At the same time, GPR56 is subject to regulation by the canonical cascade of TGF-beta 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.

引用

页数：14

共 50 条

[1] The TGF-β Signaling Pathway as a Pharmacological Target in Hepatocellular Carcinoma
Mazzocca, Antonio
Antonaci, Salvatore
Giannelli, Gianluigi
CURRENT PHARMACEUTICAL DESIGN, 2012, 18 (27) : 4148 - 4154
[2] Function of GPR56 in metastasis dormancy of melanoma
Corson, Nancy
Warren, Michelle
Xu, Lei
CANCER RESEARCH, 2016, 76
[3] The function of GPR56 in metastasis formation of melanoma
Corson, Nancy
Yang, Liquan
Xu, Lei
CANCER RESEARCH, 2016, 76
[4] POH1 contributes to hyperactivation of TGF-β signaling and facilitates hepatocellular carcinoma metastasis through deubiquitinating TGF-β receptors and caveolin-1
Wang, Boshi
Xu, Xiaoli
Yang, Zhaojuan
Zhang, Li
Liu, Yun
Ma, Aihui
Xu, Guiqin
Tang, Ming
Jing, Tiantian
Wu, Lin
Liu, Yongzhong
EBIOMEDICINE, 2019, 41 : 320 - 332
[5] CD59 facilitates tumor progression through activating TGF-β/Smad signaling pathway in hepatocellular carcinoma
Lan, Tian
Wu, Hong
CANCER RESEARCH, 2020, 80 (16)
[6] GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma
Raksha A. Ganesh
Krishnan Venkataraman
Ravi Sirdeshmukh
Journal of Cell Communication and Signaling, 2023, 17 : 1527 - 1535
[7] Inhibiting TGF-β signaling in hepatocellular carcinoma
Giannelli, Gianluigi
Mazzocca, Antonio
Fransvea, Emilia
Lahn, Michael
Antonaci, Salvatore
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2011, 1815 (02): : 214 - 223
[8] Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma
Chen, Jian
Gingold, Julian A.
Su, Xiaoping
TRENDS IN MOLECULAR MEDICINE, 2019, 25 (11) : 1010 - 1023
[9] GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma
Ganesh, Raksha A.
Venkataraman, Krishnan
Sirdeshmukh, Ravi
JOURNAL OF CELL COMMUNICATION AND SIGNALING, 2023, 17 (04) : 1527 - 1535
[10] Modulation of the TGF-β signaling pathway by long noncoding RNA in hepatocellular carcinoma
Han, Mengzhen
Liao, Zhibin
Liu, Furong
Chen, Xiaoping
Zhang, Bixiang
BIOMARKER RESEARCH, 2020, 8 (01)

← 1 2 3 4 5 →