Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production
Abstract Osteopontin (OPN) is a multifunctional cytokine that can impact cancer progression. Therefore, it is crucial to determine the key factors involved in the biological role of OPN for the development of treatment. Here, we investigated that OPN promoted hepatocellular carcinoma (HCC) cell prol...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04806-9 |
| _version_ | 1818273400503664640 |
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| author | Qipeng Wu Le Li Chunmeng Miao Muhammad Hasnat Lixin Sun Zhenzhou Jiang Luyong Zhang |
| author_facet | Qipeng Wu Le Li Chunmeng Miao Muhammad Hasnat Lixin Sun Zhenzhou Jiang Luyong Zhang |
| author_sort | Qipeng Wu |
| collection | DOAJ |
| description | Abstract Osteopontin (OPN) is a multifunctional cytokine that can impact cancer progression. Therefore, it is crucial to determine the key factors involved in the biological role of OPN for the development of treatment. Here, we investigated that OPN promoted hepatocellular carcinoma (HCC) cell proliferation and migration by increasing Reactive oxygen species (ROS) production and disclosed the underlying mechanism. Knockdown of OPN suppressed ROS production in vitro and in vivo, whereas treatment with human recombinant OPN produced the opposite effect. N-Acetyl-L-cysteine (NAC, ROS scavenger) partially blocked HCC cell proliferation and migration induced by OPN. Mechanistically, OPN induced ROS production in HCC cells by upregulating the expression of NADPH oxidase 1 (NOX1). NOX1 knockdown in HCC cells partially abrogated the cell proliferation and migration induced by OPN. Moreover, inhibition of JAK2/STAT3 phosphorylation effectively decreased the transcription of NOX1, upregulated by OPN. In addition, NOX1 overexpression increased JAK2 and STAT3 phosphorylation by increasing ROS production, creating a positive feedback loop for stimulating JAK2/STAT3 signaling induced by OPN. This study for the first time demonstrated that HCC cells utilized OPN to generate ROS for tumor progression, and disruption of OPN/NOX1 axis might be a promising therapeutic strategy for HCC. |
| first_indexed | 2024-12-12T21:57:22Z |
| format | Article |
| id | doaj.art-53a72c1662694c22ab72bd63b554621e |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-12T21:57:22Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-53a72c1662694c22ab72bd63b554621e2022-12-22T00:10:36ZengNature Publishing GroupCell Death and Disease2041-48892022-04-0113411210.1038/s41419-022-04806-9Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS productionQipeng Wu0Le Li1Chunmeng Miao2Muhammad Hasnat3Lixin Sun4Zhenzhou Jiang5Luyong Zhang6New drug screening center, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical UniversityNew drug screening center, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical UniversityNew drug screening center, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical UniversityInstitute of Pharmaceutical Sciences, University of Veterinary and Animal SciencesNew drug screening center, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical UniversityNew drug screening center, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical UniversityNew drug screening center, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical UniversityAbstract Osteopontin (OPN) is a multifunctional cytokine that can impact cancer progression. Therefore, it is crucial to determine the key factors involved in the biological role of OPN for the development of treatment. Here, we investigated that OPN promoted hepatocellular carcinoma (HCC) cell proliferation and migration by increasing Reactive oxygen species (ROS) production and disclosed the underlying mechanism. Knockdown of OPN suppressed ROS production in vitro and in vivo, whereas treatment with human recombinant OPN produced the opposite effect. N-Acetyl-L-cysteine (NAC, ROS scavenger) partially blocked HCC cell proliferation and migration induced by OPN. Mechanistically, OPN induced ROS production in HCC cells by upregulating the expression of NADPH oxidase 1 (NOX1). NOX1 knockdown in HCC cells partially abrogated the cell proliferation and migration induced by OPN. Moreover, inhibition of JAK2/STAT3 phosphorylation effectively decreased the transcription of NOX1, upregulated by OPN. In addition, NOX1 overexpression increased JAK2 and STAT3 phosphorylation by increasing ROS production, creating a positive feedback loop for stimulating JAK2/STAT3 signaling induced by OPN. This study for the first time demonstrated that HCC cells utilized OPN to generate ROS for tumor progression, and disruption of OPN/NOX1 axis might be a promising therapeutic strategy for HCC.https://doi.org/10.1038/s41419-022-04806-9 |
| spellingShingle | Qipeng Wu Le Li Chunmeng Miao Muhammad Hasnat Lixin Sun Zhenzhou Jiang Luyong Zhang Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production Cell Death and Disease |
| title | Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production |
| title_full | Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production |
| title_fullStr | Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production |
| title_full_unstemmed | Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production |
| title_short | Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production |
| title_sort | osteopontin promotes hepatocellular carcinoma progression through inducing jak2 stat3 nox1 mediated ros production |
| url | https://doi.org/10.1038/s41419-022-04806-9 |
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