FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1
Immune-checkpoint blockade (ICB) therapies have been widely used in clinical treatment of cancer patients, but only 20–30% of patients benefit from immunotherapy. Therefore, it is important to decipher the molecular mechanism of resistance to ICB and develop new combined treatment strategies. PD-L1...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223017535 |
| _version_ | 1797364271604039680 |
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| author | Chaoqin Guo Nana Zhou Yisong Lu Mingshan Mu Zilin Li Xu Zhang Linglan Tu Jingyang Du Xiangyu Li Dongsheng Huang Qiuran Xu Xiaoliang Zheng |
| author_facet | Chaoqin Guo Nana Zhou Yisong Lu Mingshan Mu Zilin Li Xu Zhang Linglan Tu Jingyang Du Xiangyu Li Dongsheng Huang Qiuran Xu Xiaoliang Zheng |
| author_sort | Chaoqin Guo |
| collection | DOAJ |
| description | Immune-checkpoint blockade (ICB) therapies have been widely used in clinical treatment of cancer patients, but only 20–30% of patients benefit from immunotherapy. Therefore, it is important to decipher the molecular mechanism of resistance to ICB and develop new combined treatment strategies. PD-L1 up-regulation in tumor cells contributes to the occurrence of immune escape. Increasing evidence shows that its transcription level is affected by multiple factors, which limits the objective response rate of ICB. Fibroblast growth factor 19 (FGF19), a member of the fibroblast growth factor family, is widely involved in the malignant progression of many tumors by binding to fibroblast growth factor receptor 4 (FGFR4). In this study, we confirmed that FGF19 acts as a driver gene in hepatocellular carcinoma (HCC) progression by binding to FGFR4. The up-regulation of FGF19 and FGFR4 in HCC is associated with poor prognosis. We found that FGF19/FGFR4 promoted the proliferation and invasion of HCC cells by driving IGF2BP1 to promote PD-L1 expression. Knockdown of FGFR4 significantly reduced the expression of IGF2BP1/PD-L1 and inhibited the proliferation and invasion of HCC cells. These biological effects are achieved by inhibiting the PI3K/AKT pathway. The combination of FGFR4 knockdown and anti-PD-1 antibody greatly suppressed tumor growth and enhanced the sensitivity of immunotherapy, highlighting the clinical significance of FGF19/FGFR4 activation in immunotherapy. |
| first_indexed | 2024-03-08T16:32:53Z |
| format | Article |
| id | doaj.art-0c6ad0c2d1ac41acb57e8b88b8cd754a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-08T16:32:53Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-0c6ad0c2d1ac41acb57e8b88b8cd754a2024-01-06T04:37:41ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-01-01170115955FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1Chaoqin Guo0Nana Zhou1Yisong Lu2Mingshan Mu3Zilin Li4Xu Zhang5Linglan Tu6Jingyang Du7Xiangyu Li8Dongsheng Huang9Qiuran Xu10Xiaoliang Zheng11School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 310053, ChinaThe Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Corresponding authors.The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Corresponding authors.School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 310053, China; Zhejiang Provincial Laboratory of Experimental Animal’s & Nonclinical Laboratory Studies, Hangzhou Medical College, Hangzhou 310053, China; Corresponding author at: School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 310053, China.Immune-checkpoint blockade (ICB) therapies have been widely used in clinical treatment of cancer patients, but only 20–30% of patients benefit from immunotherapy. Therefore, it is important to decipher the molecular mechanism of resistance to ICB and develop new combined treatment strategies. PD-L1 up-regulation in tumor cells contributes to the occurrence of immune escape. Increasing evidence shows that its transcription level is affected by multiple factors, which limits the objective response rate of ICB. Fibroblast growth factor 19 (FGF19), a member of the fibroblast growth factor family, is widely involved in the malignant progression of many tumors by binding to fibroblast growth factor receptor 4 (FGFR4). In this study, we confirmed that FGF19 acts as a driver gene in hepatocellular carcinoma (HCC) progression by binding to FGFR4. The up-regulation of FGF19 and FGFR4 in HCC is associated with poor prognosis. We found that FGF19/FGFR4 promoted the proliferation and invasion of HCC cells by driving IGF2BP1 to promote PD-L1 expression. Knockdown of FGFR4 significantly reduced the expression of IGF2BP1/PD-L1 and inhibited the proliferation and invasion of HCC cells. These biological effects are achieved by inhibiting the PI3K/AKT pathway. The combination of FGFR4 knockdown and anti-PD-1 antibody greatly suppressed tumor growth and enhanced the sensitivity of immunotherapy, highlighting the clinical significance of FGF19/FGFR4 activation in immunotherapy.http://www.sciencedirect.com/science/article/pii/S0753332223017535Hepatocellular carcionomaImmune evasionPD-L1FGF19/FGFR4IGF2BP1 |
| spellingShingle | Chaoqin Guo Nana Zhou Yisong Lu Mingshan Mu Zilin Li Xu Zhang Linglan Tu Jingyang Du Xiangyu Li Dongsheng Huang Qiuran Xu Xiaoliang Zheng FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1 Biomedicine & Pharmacotherapy Hepatocellular carcionoma Immune evasion PD-L1 FGF19/FGFR4 IGF2BP1 |
| title | FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1 |
| title_full | FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1 |
| title_fullStr | FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1 |
| title_full_unstemmed | FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1 |
| title_short | FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1 |
| title_sort | fgf19 fgfr4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating igf2bp1 mediated expression of pd l1 |
| topic | Hepatocellular carcionoma Immune evasion PD-L1 FGF19/FGFR4 IGF2BP1 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223017535 |
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