ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells
Abstract Molecular signatures are increasingly recognized as pivotal factors in therapy selection for lung adenocarcinomas (LUAD). A developing therapeutic approach focuses on targeting metabolic dependencies within cancer cells. ERCC6L, a vital protein involved in chromosome separation during cell...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07879-4 |
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| author | Zhimin Lu Xuming Yao Jialu Jiang Guoxin Hou |
| author_facet | Zhimin Lu Xuming Yao Jialu Jiang Guoxin Hou |
| author_sort | Zhimin Lu |
| collection | DOAJ |
| description | Abstract Molecular signatures are increasingly recognized as pivotal factors in therapy selection for lung adenocarcinomas (LUAD). A developing therapeutic approach focuses on targeting metabolic dependencies within cancer cells. ERCC6L, a vital protein involved in chromosome separation during cell mitosis, emerges as a compelling subject concerning its impact on LUAD tumorigenesis and progression. Our investigation uncovered elevated levels of ERCC6L in LUAD, significantly associated with unfavorable patient outcomes. Functional analyses elucidate ERCC6L’s role in promoting LUAD cell proliferation, migration, and invasion by inducing glycolysis and stemness characteristics. Mechanistically, our data reveal ERCC6L’s involvement in upregulating aerobic glycolysis through the induction of hypoxia-inducible factor-1α (HIF-1α) expression and transcriptional activity in LUAD cells. Furthermore, ERCC6L stabilizes HIF-1α by inhibiting its hydroxylation and ubiquitin-mediated degradation. The ERCC6L/HIF-1α axis plays a crucial functional role in enhancing cancer stemness and LUAD progression both in vitro and in vivo. Hence, our findings underscore the significance of the ERCC6L/HIF-1α axis in regulating aerobic glycolysis in LUAD cells, suggesting its potential as a biomarker and therapeutic target for LUAD patients. |
| format | Article |
| id | doaj-art-0feb5a4c9be5491cbeedb5a8b5d4c37c |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-0feb5a4c9be5491cbeedb5a8b5d4c37c2025-08-20T03:42:10ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111410.1038/s41419-025-07879-4ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cellsZhimin Lu0Xuming Yao1Jialu Jiang2Guoxin Hou3Department of Outpatient, Affiliated Hospital of Jiaxing University, The First Hospital of JiaxingDepartment of Oncology, Affiliated Hospital of Jiaxing University, The First Hospital of JiaxingDepartment of Oncology, Affiliated Hospital of Jiaxing University, The First Hospital of JiaxingDepartment of Oncology, Affiliated Hospital of Jiaxing University, The First Hospital of JiaxingAbstract Molecular signatures are increasingly recognized as pivotal factors in therapy selection for lung adenocarcinomas (LUAD). A developing therapeutic approach focuses on targeting metabolic dependencies within cancer cells. ERCC6L, a vital protein involved in chromosome separation during cell mitosis, emerges as a compelling subject concerning its impact on LUAD tumorigenesis and progression. Our investigation uncovered elevated levels of ERCC6L in LUAD, significantly associated with unfavorable patient outcomes. Functional analyses elucidate ERCC6L’s role in promoting LUAD cell proliferation, migration, and invasion by inducing glycolysis and stemness characteristics. Mechanistically, our data reveal ERCC6L’s involvement in upregulating aerobic glycolysis through the induction of hypoxia-inducible factor-1α (HIF-1α) expression and transcriptional activity in LUAD cells. Furthermore, ERCC6L stabilizes HIF-1α by inhibiting its hydroxylation and ubiquitin-mediated degradation. The ERCC6L/HIF-1α axis plays a crucial functional role in enhancing cancer stemness and LUAD progression both in vitro and in vivo. Hence, our findings underscore the significance of the ERCC6L/HIF-1α axis in regulating aerobic glycolysis in LUAD cells, suggesting its potential as a biomarker and therapeutic target for LUAD patients.https://doi.org/10.1038/s41419-025-07879-4 |
| spellingShingle | Zhimin Lu Xuming Yao Jialu Jiang Guoxin Hou ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells Cell Death and Disease |
| title | ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells |
| title_full | ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells |
| title_fullStr | ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells |
| title_full_unstemmed | ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells |
| title_short | ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells |
| title_sort | ercc6l mediated stabilization of hif 1α enhances glycolysis and stemness properties of lung adenocarcinoma cells |
| url | https://doi.org/10.1038/s41419-025-07879-4 |
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