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F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production
BACKGROUND: Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC microenvironment remains elusive. METHODS: We used bioinformatics and clinical sample ana...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900488/ https://www.ncbi.nlm.nih.gov/pubmed/36709580 http://dx.doi.org/10.1016/j.ebiom.2023.104444 |
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author | Sun, Jiwei Tang, Qingming Yu, Shaoling Xie, Mengru Zheng, Wenhao Chen, Guangjin Yin, Ying Huang, Xiaofei Wo, Keqi Lei, Haoqi Zhang, Junyuan Wan, Qian Chen, Lili |
author_facet | Sun, Jiwei Tang, Qingming Yu, Shaoling Xie, Mengru Zheng, Wenhao Chen, Guangjin Yin, Ying Huang, Xiaofei Wo, Keqi Lei, Haoqi Zhang, Junyuan Wan, Qian Chen, Lili |
author_sort | Sun, Jiwei |
collection | PubMed |
description | BACKGROUND: Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC microenvironment remains elusive. METHODS: We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum. FINDINGS: We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression. INTERPRETATION: These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC. FUNDING: This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC). |
format | Online Article Text |
id | pubmed-9900488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99004882023-02-07 F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production Sun, Jiwei Tang, Qingming Yu, Shaoling Xie, Mengru Zheng, Wenhao Chen, Guangjin Yin, Ying Huang, Xiaofei Wo, Keqi Lei, Haoqi Zhang, Junyuan Wan, Qian Chen, Lili eBioMedicine Articles BACKGROUND: Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC microenvironment remains elusive. METHODS: We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum. FINDINGS: We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression. INTERPRETATION: These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC. FUNDING: This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC). Elsevier 2023-01-27 /pmc/articles/PMC9900488/ /pubmed/36709580 http://dx.doi.org/10.1016/j.ebiom.2023.104444 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Sun, Jiwei Tang, Qingming Yu, Shaoling Xie, Mengru Zheng, Wenhao Chen, Guangjin Yin, Ying Huang, Xiaofei Wo, Keqi Lei, Haoqi Zhang, Junyuan Wan, Qian Chen, Lili F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production |
title | F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production |
title_full | F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production |
title_fullStr | F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production |
title_full_unstemmed | F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production |
title_short | F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production |
title_sort | f. nucleatum facilitates oral squamous cell carcinoma progression via glut1-driven lactate production |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900488/ https://www.ncbi.nlm.nih.gov/pubmed/36709580 http://dx.doi.org/10.1016/j.ebiom.2023.104444 |
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