Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway
Vesicle Protein Sorting 35 (VPS35) is a novel oncogene that promotes tumor growth through the PI3K/AKT signaling in hepatocellular carcinoma (HCC). However, the role of VPS35 in HCC metastasis and the underlying mechanisms remain largely unclear. In this study, we observed that overexpression of VPS...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2021-03-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300921 |
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| author | Yi Liu Haijun Deng Li Liang Guiji Zhang Jie Xia Keyue Ding Ni Tang Kai Wang |
| author_facet | Yi Liu Haijun Deng Li Liang Guiji Zhang Jie Xia Keyue Ding Ni Tang Kai Wang |
| author_sort | Yi Liu |
| collection | DOAJ |
| description | Vesicle Protein Sorting 35 (VPS35) is a novel oncogene that promotes tumor growth through the PI3K/AKT signaling in hepatocellular carcinoma (HCC). However, the role of VPS35 in HCC metastasis and the underlying mechanisms remain largely unclear. In this study, we observed that overexpression of VPS35 enhanced hepatoma cell invasion and metastasis by inducing epithelial–mesenchymal transition (EMT)-related gene expression. Conversely, knockout of VPS35 significantly inhibited hepatoma cell migration and invasion. Furthermore, depletion of VPS35 decreased the lung metastasis of HCC in nude mice. By transcriptome analysis, we determined that VPS35 promoted HCC metastasis by activating the Wnt/non-canonical planar cell polarity (PCP) pathway. Mechanistically, VPS35 activated the PCP pathway by regulating membrane sorting and trafficking of Frizzled-2 (FZD2) and ROR1 in hepatoma cells. Collectively, our results indicate that VPS35 promotes HCC metastasis via enhancing the Wnt/PCP signaling, thus providing a potential prognostic marker and therapeutic target for HCC. |
| first_indexed | 2024-03-12T19:02:36Z |
| format | Article |
| id | doaj.art-b4809dca3f8247d1984d72def20894f7 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T19:02:36Z |
| publishDate | 2021-03-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Genes and Diseases |
| spelling | doaj.art-b4809dca3f8247d1984d72def20894f72023-08-02T06:30:04ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422021-03-0182232240Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathwayYi Liu0Haijun Deng1Li Liang2Guiji Zhang3Jie Xia4Keyue Ding5Ni Tang6Kai Wang7Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR ChinaDepartment of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR China; Corresponding author.Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR China; Corresponding author.Vesicle Protein Sorting 35 (VPS35) is a novel oncogene that promotes tumor growth through the PI3K/AKT signaling in hepatocellular carcinoma (HCC). However, the role of VPS35 in HCC metastasis and the underlying mechanisms remain largely unclear. In this study, we observed that overexpression of VPS35 enhanced hepatoma cell invasion and metastasis by inducing epithelial–mesenchymal transition (EMT)-related gene expression. Conversely, knockout of VPS35 significantly inhibited hepatoma cell migration and invasion. Furthermore, depletion of VPS35 decreased the lung metastasis of HCC in nude mice. By transcriptome analysis, we determined that VPS35 promoted HCC metastasis by activating the Wnt/non-canonical planar cell polarity (PCP) pathway. Mechanistically, VPS35 activated the PCP pathway by regulating membrane sorting and trafficking of Frizzled-2 (FZD2) and ROR1 in hepatoma cells. Collectively, our results indicate that VPS35 promotes HCC metastasis via enhancing the Wnt/PCP signaling, thus providing a potential prognostic marker and therapeutic target for HCC.http://www.sciencedirect.com/science/article/pii/S2352304220300921Epithelial–mesenchymal transitionHepatocellular carcinoma (HCC)MetastasisRetromer complexVPS35Wnt/PCP signaling pathway |
| spellingShingle | Yi Liu Haijun Deng Li Liang Guiji Zhang Jie Xia Keyue Ding Ni Tang Kai Wang Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway Genes and Diseases Epithelial–mesenchymal transition Hepatocellular carcinoma (HCC) Metastasis Retromer complex VPS35 Wnt/PCP signaling pathway |
| title | Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway |
| title_full | Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway |
| title_fullStr | Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway |
| title_full_unstemmed | Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway |
| title_short | Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway |
| title_sort | depletion of vps35 attenuates metastasis of hepatocellular carcinoma by restraining the wnt pcp signaling pathway |
| topic | Epithelial–mesenchymal transition Hepatocellular carcinoma (HCC) Metastasis Retromer complex VPS35 Wnt/PCP signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220300921 |
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