Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma.
Alternative Lengthening of Telomeres (ALT) is a telomerase-independent mechanism deployed by several aggressive cancers to maintain telomere length. This contributes to their malignancy and resistance to conventional therapies. In prior studies, we have identified key proteins linked to the ALT proc...
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Public Library of Science (PLoS)
2025-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0314012 |
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| author | Isaac Armendáriz-Castillo Jennyfer García-Cárdenas Pamela Espinosa Katherine Hidalgo-Fernández Lizbeth Peña-Zúñiga Ronie Martínez Juan Moromenacho Andrés Herrera-Yela Jonathan Cruz-Varela Anilú Saucedo-Sariñana María-Esperanza Cerdán Andrés López-Cortés Santiago Guerrero |
| author_facet | Isaac Armendáriz-Castillo Jennyfer García-Cárdenas Pamela Espinosa Katherine Hidalgo-Fernández Lizbeth Peña-Zúñiga Ronie Martínez Juan Moromenacho Andrés Herrera-Yela Jonathan Cruz-Varela Anilú Saucedo-Sariñana María-Esperanza Cerdán Andrés López-Cortés Santiago Guerrero |
| author_sort | Isaac Armendáriz-Castillo |
| collection | DOAJ |
| description | Alternative Lengthening of Telomeres (ALT) is a telomerase-independent mechanism deployed by several aggressive cancers to maintain telomere length. This contributes to their malignancy and resistance to conventional therapies. In prior studies, we have identified key proteins linked to the ALT process using multi-omic data integration strategies. In this work, we combined metabolomic datasets with our earlier results to identify targetable metabolic pathways for ALT-positive tumors. 39 ALT-related proteins were found to interact with 42 different metabolites in our analysis. Additional networking analysis revealed a complex interaction between metabolites and ALT-related proteins, suggesting that pan-cancer oncogenes may have an impact on these pathways. Three metabolic pathways have been primarily related with the ALT mechanism: purine metabolism, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism. Lastly, we prioritized FDA-approved drugs (azathioprine, thioguanine, and mercaptopurine) that could target ALT-positive tumors through purine metabolism. This work provides a wide perspective of the metabolomic pathways associated with ALT and reveals potential therapeutic targets that require further experimental validation. |
| format | Article |
| id | doaj-art-8d1e5d20b1ed4836add4fb10a308db7e |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8d1e5d20b1ed4836add4fb10a308db7e2025-08-20T02:15:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e031401210.1371/journal.pone.0314012Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma.Isaac Armendáriz-CastilloJennyfer García-CárdenasPamela EspinosaKatherine Hidalgo-FernándezLizbeth Peña-ZúñigaRonie MartínezJuan MoromenachoAndrés Herrera-YelaJonathan Cruz-VarelaAnilú Saucedo-SariñanaMaría-Esperanza CerdánAndrés López-CortésSantiago GuerreroAlternative Lengthening of Telomeres (ALT) is a telomerase-independent mechanism deployed by several aggressive cancers to maintain telomere length. This contributes to their malignancy and resistance to conventional therapies. In prior studies, we have identified key proteins linked to the ALT process using multi-omic data integration strategies. In this work, we combined metabolomic datasets with our earlier results to identify targetable metabolic pathways for ALT-positive tumors. 39 ALT-related proteins were found to interact with 42 different metabolites in our analysis. Additional networking analysis revealed a complex interaction between metabolites and ALT-related proteins, suggesting that pan-cancer oncogenes may have an impact on these pathways. Three metabolic pathways have been primarily related with the ALT mechanism: purine metabolism, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism. Lastly, we prioritized FDA-approved drugs (azathioprine, thioguanine, and mercaptopurine) that could target ALT-positive tumors through purine metabolism. This work provides a wide perspective of the metabolomic pathways associated with ALT and reveals potential therapeutic targets that require further experimental validation.https://doi.org/10.1371/journal.pone.0314012 |
| spellingShingle | Isaac Armendáriz-Castillo Jennyfer García-Cárdenas Pamela Espinosa Katherine Hidalgo-Fernández Lizbeth Peña-Zúñiga Ronie Martínez Juan Moromenacho Andrés Herrera-Yela Jonathan Cruz-Varela Anilú Saucedo-Sariñana María-Esperanza Cerdán Andrés López-Cortés Santiago Guerrero Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma. PLoS ONE |
| title | Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma. |
| title_full | Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma. |
| title_fullStr | Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma. |
| title_full_unstemmed | Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma. |
| title_short | Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma. |
| title_sort | metabolic pathways of alternative lengthening of telomeres in pan carcinoma |
| url | https://doi.org/10.1371/journal.pone.0314012 |
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