SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer
Abstract Vasculogenic mimicry (VM), a new model of angiogenesis, fulfills the metabolic demands of solid tumors and contributes to tumor aggressiveness. Our previous study demonstrated the effect of SOX2 in promoting VM in colorectal cancer (CRC). However, the underlying mechanisms behind this effec...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06274-1 |
| _version_ | 1797397781415985152 |
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| author | Shimiao Huang Xuan Wang Yin Zhu Yadong Wang Jiaxuan Chen Haoxuan Zheng |
| author_facet | Shimiao Huang Xuan Wang Yin Zhu Yadong Wang Jiaxuan Chen Haoxuan Zheng |
| author_sort | Shimiao Huang |
| collection | DOAJ |
| description | Abstract Vasculogenic mimicry (VM), a new model of angiogenesis, fulfills the metabolic demands of solid tumors and contributes to tumor aggressiveness. Our previous study demonstrated the effect of SOX2 in promoting VM in colorectal cancer (CRC). However, the underlying mechanisms behind this effect remain elusive. Here, we show that SOX2 overexpression enhanced glycolysis and sustained VM formation via the transcriptional activation of lncRNA AC005392.2. Suppression of either glycolysis or AC005392.2 expression curbed SOX2-driven VM formation in vivo and in vitro. Mechanistically, SOX2 combined with the promoter of AC005392.2, which decreased H3K27me3 enrichment and thus increased its transcriptional activity. Overexpression of AC005392.2 increased the stability of GLUT1 protein by enhancing its SUMOylation, leading to a decrease in the ubiquitination and degradation of GLUT1. Accumulation of GLUT1 contributed to SOX2-mediated glycolysis and VM. Additionally, clinical analyses showed that increased levels of AC005392.2, GLUT1, and EPHA2 expression were positively correlated with SOX2 and were also associated with poor prognoses in patients with CRC. Our study conclusively demonstrates that the SOX2-lncRNA AC005392.2-GLUT1 signaling axis regulates VM formation in CRC, offering a foundation for the development of new antiangiogenic drugs or new drug combination regimens. |
| first_indexed | 2024-03-09T01:15:06Z |
| format | Article |
| id | doaj.art-debfc655e56c4c598fafffe25c3fd5e7 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-09T01:15:06Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-debfc655e56c4c598fafffe25c3fd5e72023-12-10T12:33:25ZengNature Publishing GroupCell Death and Disease2041-48892023-12-01141211210.1038/s41419-023-06274-1SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancerShimiao Huang0Xuan Wang1Yin Zhu2Yadong Wang3Jiaxuan Chen4Haoxuan Zheng5Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversitySchool of Laboratory Medicine and Biotechnology, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityState Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityAbstract Vasculogenic mimicry (VM), a new model of angiogenesis, fulfills the metabolic demands of solid tumors and contributes to tumor aggressiveness. Our previous study demonstrated the effect of SOX2 in promoting VM in colorectal cancer (CRC). However, the underlying mechanisms behind this effect remain elusive. Here, we show that SOX2 overexpression enhanced glycolysis and sustained VM formation via the transcriptional activation of lncRNA AC005392.2. Suppression of either glycolysis or AC005392.2 expression curbed SOX2-driven VM formation in vivo and in vitro. Mechanistically, SOX2 combined with the promoter of AC005392.2, which decreased H3K27me3 enrichment and thus increased its transcriptional activity. Overexpression of AC005392.2 increased the stability of GLUT1 protein by enhancing its SUMOylation, leading to a decrease in the ubiquitination and degradation of GLUT1. Accumulation of GLUT1 contributed to SOX2-mediated glycolysis and VM. Additionally, clinical analyses showed that increased levels of AC005392.2, GLUT1, and EPHA2 expression were positively correlated with SOX2 and were also associated with poor prognoses in patients with CRC. Our study conclusively demonstrates that the SOX2-lncRNA AC005392.2-GLUT1 signaling axis regulates VM formation in CRC, offering a foundation for the development of new antiangiogenic drugs or new drug combination regimens.https://doi.org/10.1038/s41419-023-06274-1 |
| spellingShingle | Shimiao Huang Xuan Wang Yin Zhu Yadong Wang Jiaxuan Chen Haoxuan Zheng SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer Cell Death and Disease |
| title | SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer |
| title_full | SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer |
| title_fullStr | SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer |
| title_full_unstemmed | SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer |
| title_short | SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer |
| title_sort | sox2 promotes vasculogenic mimicry by accelerating glycolysis via the lncrna ac005392 2 glut1 axis in colorectal cancer |
| url | https://doi.org/10.1038/s41419-023-06274-1 |
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