Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma
Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cell...
| Huvudupphovsmän: | , , , , , |
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| Materialtyp: | Artikel |
| Språk: | English |
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American Association for the Advancement of Science (AAAS)
2024-01-01
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| Serie: | Research |
| Länkar: | https://spj.science.org/doi/10.34133/research.0425 |
| _version_ | 1827186732862275584 |
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| author | Yiming Liu Xinyang Hu Sining Zhou Ting Sun Feiyan Shen Linghui Zeng |
| author_facet | Yiming Liu Xinyang Hu Sining Zhou Ting Sun Feiyan Shen Linghui Zeng |
| author_sort | Yiming Liu |
| collection | DOAJ |
| description | Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras–mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC. |
| first_indexed | 2025-03-21T07:10:58Z |
| format | Article |
| id | doaj.art-5a93b51a82c64c8685fe02d47f4fccef |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2025-03-21T07:10:58Z |
| publishDate | 2024-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-5a93b51a82c64c8685fe02d47f4fccef2024-07-17T00:09:59ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742024-01-01710.34133/research.0425Golgi Protein 73 Promotes Angiogenesis in Hepatocellular CarcinomaYiming Liu0Xinyang Hu1Sining Zhou2Ting Sun3Feiyan Shen4Linghui Zeng5Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Hangzhou City University School of Medicine, Hangzhou 310015, China.Laboratory of Cancer Biology, Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310017, China.Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Hangzhou City University School of Medicine, Hangzhou 310015, China.Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Hangzhou City University School of Medicine, Hangzhou 310015, China.Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras–mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.https://spj.science.org/doi/10.34133/research.0425 |
| spellingShingle | Yiming Liu Xinyang Hu Sining Zhou Ting Sun Feiyan Shen Linghui Zeng Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma Research |
| title | Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma |
| title_full | Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma |
| title_fullStr | Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma |
| title_full_unstemmed | Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma |
| title_short | Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma |
| title_sort | golgi protein 73 promotes angiogenesis in hepatocellular carcinoma |
| url | https://spj.science.org/doi/10.34133/research.0425 |
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