Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression
Abstract Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not...
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Nature Publishing Group
2025-01-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-024-00326-8 |
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| author | Camila Paz Muñoz-Grez Mabel Angélica Vidal Tamara Beatriz Rojas Luciano Esteban Ferrada Felipe Andrés Zuñiga Agustin Andrés Vera Sergio Andrés Sanhueza Romina Andrea Quiroga Camilo Daniel Cabrera Barbara Evelyn Antilef Ricardo Andrés Cartes Milovan Paolo Acevedo Marco Andrés Fraga Pedro Felipe Alarcón-Zapata Mauricio Alejandro Hernández Alexis Marcelo Salas-Burgos Francisco Tapia-Belmonte Milly Loreto Yáñez Erick Marcelo Riquelme Wilfredo Alejandro González Cesar Andrés Rivera Angel Alejandro Oñate Liliana Ivonne Lamperti Estefanía Nova-Lamperti |
| author_facet | Camila Paz Muñoz-Grez Mabel Angélica Vidal Tamara Beatriz Rojas Luciano Esteban Ferrada Felipe Andrés Zuñiga Agustin Andrés Vera Sergio Andrés Sanhueza Romina Andrea Quiroga Camilo Daniel Cabrera Barbara Evelyn Antilef Ricardo Andrés Cartes Milovan Paolo Acevedo Marco Andrés Fraga Pedro Felipe Alarcón-Zapata Mauricio Alejandro Hernández Alexis Marcelo Salas-Burgos Francisco Tapia-Belmonte Milly Loreto Yáñez Erick Marcelo Riquelme Wilfredo Alejandro González Cesar Andrés Rivera Angel Alejandro Oñate Liliana Ivonne Lamperti Estefanía Nova-Lamperti |
| author_sort | Camila Paz Muñoz-Grez |
| collection | DOAJ |
| description | Abstract Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood. In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome. The main host-pathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry. Then, functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer. Host proteins associated with LPS response, cell migration/adhesion, and metabolism of amino acids were significantly upregulated in the human cancer proteome, whereas the complement cascade was downregulated in malignant samples. Then, the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum (F. nucleatum) in OSCC samples, from which several enzymes from the L-glutamate degradation pathway were found, indicating that L-glutamate from cancer cells is used as an energy source, and catabolized into butyrate by the bacteria. In fact, we observed that F. nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression, promoting L-glutamate efflux and favoring bacterial infection. Finally, our results showed that F. nucleatum and its metabolic derivates promote tumor spheroids growth, spheroids-derived cell detachment, epithelial-mesenchymal transition and Galectin-9 upregulation. Altogether, F. nucleatum promotes pro-tumoral mechanism in oral cancer. |
| format | Article |
| id | doaj-art-096e8fb37a884944bd7a4073b196b747 |
| institution | Kabale University |
| issn | 2049-3169 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
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| series | International Journal of Oral Science |
| spelling | doaj-art-096e8fb37a884944bd7a4073b196b7472025-01-05T12:10:20ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-01-0117111410.1038/s41368-024-00326-8Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progressionCamila Paz Muñoz-Grez0Mabel Angélica Vidal1Tamara Beatriz Rojas2Luciano Esteban Ferrada3Felipe Andrés Zuñiga4Agustin Andrés Vera5Sergio Andrés Sanhueza6Romina Andrea Quiroga7Camilo Daniel Cabrera8Barbara Evelyn Antilef9Ricardo Andrés Cartes10Milovan Paolo Acevedo11Marco Andrés Fraga12Pedro Felipe Alarcón-Zapata13Mauricio Alejandro HernándezAlexis Marcelo Salas-Burgos14Francisco Tapia-Belmonte15Milly Loreto Yáñez16Erick Marcelo Riquelme17Wilfredo Alejandro González18Cesar Andrés Rivera19Angel Alejandro Oñate20Liliana Ivonne Lamperti21Estefanía Nova-Lamperti22Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónFacultad de Ingeniería, Universidad de TalcaCMA BIO BIO, Faculty of Biological Sciences, Universidad de ConcepciónBIOTER Laboratory, Clinical Biochemistry and Immunology Department, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónBIOTER Laboratory, Clinical Biochemistry and Immunology Department, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónDepartment of Pharmacology, Faculty of Biological Sciences, Universidad de ConcepcionCancer Molecular Dynamics Laboratory, Pharmacology Department, Faculty of Biological Sciences, Universidad de ConcepciónCancer Molecular Dynamics Laboratory, Pharmacology Department, Faculty of Biological Sciences, Universidad de ConcepciónAnatomy Pathology Unit and Dental Service, Oral Pathology Department, Hospital Las HiguerasRespiratory diseases Department, Faculty of Medicine, Pontifical University Catholic of ChileDentistry Faculty, Universidad de los AndesOral Medicine and Pathology Research Group, Faculty of Health Sciences, Universidad de TalcaLaboratory of Molecular Immunology, Department of Microbiology, Faculty of Biological Sciences, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de ConcepciónAbstract Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood. In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome. The main host-pathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry. Then, functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer. Host proteins associated with LPS response, cell migration/adhesion, and metabolism of amino acids were significantly upregulated in the human cancer proteome, whereas the complement cascade was downregulated in malignant samples. Then, the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum (F. nucleatum) in OSCC samples, from which several enzymes from the L-glutamate degradation pathway were found, indicating that L-glutamate from cancer cells is used as an energy source, and catabolized into butyrate by the bacteria. In fact, we observed that F. nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression, promoting L-glutamate efflux and favoring bacterial infection. Finally, our results showed that F. nucleatum and its metabolic derivates promote tumor spheroids growth, spheroids-derived cell detachment, epithelial-mesenchymal transition and Galectin-9 upregulation. Altogether, F. nucleatum promotes pro-tumoral mechanism in oral cancer.https://doi.org/10.1038/s41368-024-00326-8 |
| spellingShingle | Camila Paz Muñoz-Grez Mabel Angélica Vidal Tamara Beatriz Rojas Luciano Esteban Ferrada Felipe Andrés Zuñiga Agustin Andrés Vera Sergio Andrés Sanhueza Romina Andrea Quiroga Camilo Daniel Cabrera Barbara Evelyn Antilef Ricardo Andrés Cartes Milovan Paolo Acevedo Marco Andrés Fraga Pedro Felipe Alarcón-Zapata Mauricio Alejandro Hernández Alexis Marcelo Salas-Burgos Francisco Tapia-Belmonte Milly Loreto Yáñez Erick Marcelo Riquelme Wilfredo Alejandro González Cesar Andrés Rivera Angel Alejandro Oñate Liliana Ivonne Lamperti Estefanía Nova-Lamperti Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression International Journal of Oral Science |
| title | Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression |
| title_full | Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression |
| title_fullStr | Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression |
| title_full_unstemmed | Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression |
| title_short | Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression |
| title_sort | host microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between fusobacterium nucleatum and cancer progression |
| url | https://doi.org/10.1038/s41368-024-00326-8 |
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