Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression.

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

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Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression.

Author: Camila Paz MUÑOZ-GREZ ¹ ; Mabel Angélica VIDAL ¹ ; Tamara Beatriz ROJAS ² ; Luciano Esteban FERRADA ³ ; Felipe Andrés ZUÑIGA ⁴ ; Agustin Andrés VERA ¹ ; Sergio Andrés SANHUEZA ¹ ; Romina Andrea QUIROGA ¹ ; Camilo Daniel CABRERA ¹ ; Barbara Evelyn ANTILEF ¹ ; Ricardo Andrés CARTES ¹ ; Milovan Paolo ACEVEDO ⁴ ; Marco Andrés FRAGA ¹ ; Pedro Felipe ALARCÓN-ZAPATA ⁵ ; Mauricio Alejandro HERNÁNDEZ ⁶ ; Alexis Marcelo SALAS-BURGOS ⁷ ; Francisco TAPIA-BELMONTE ⁷ ; Milly Loreto YÁÑEZ ⁸ ; Erick Marcelo RIQUELME ⁹ ; Wilfredo Alejandro GONZÁLEZ ¹⁰ ; Cesar Andrés RIVERA ¹¹ ; Angel Alejandro OÑATE ¹² ; Liliana Ivonne LAMPERTI ¹ ; Estefanía NOVA-LAMPERTI ¹³
Author Information

1. Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de Concepción, Concepción, Chile.
2. Facultad de Ingeniería, Universidad de Talca, Talca, Chile.
3. CMA BIO BIO, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile.
4. BIOTER Laboratory, Clinical Biochemistry and Immunology Department, Pharmacy Faculty, Universidad de Concepción, Concepción, Chile.
5. Department of Pharmacology, Faculty of Biological Sciences, Universidad de Concepcion, Concepción, Chile.
6. , MELISA Institute, San Pedro de la Paz, Chile.
7. Cancer Molecular Dynamics Laboratory, Pharmacology Department, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile.
8. Anatomy Pathology Unit and Dental Service, Oral Pathology Department, Hospital Las Higueras, Talcahuano, Chile.
9. Respiratory diseases Department, Faculty of Medicine, Pontifical University Catholic of Chile, Santiago, Chile.
10. Dentistry Faculty, Universidad de los Andes, Santiago, Chile.
11. Oral Medicine and Pathology Research Group, Faculty of Health Sciences, Universidad de Talca, Talca, Chile.
12. Laboratory of Molecular Immunology, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile.
13. Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, Universidad de Concepción, Concepción, Chile. enovalamperti@gmail.com.
Publication Type:Research Support, Non-U.S. Gov't
MeSH: Humans; Fusobacterium nucleatum/metabolism*; Mouth Neoplasms/metabolism*; Disease Progression; Proteomics; Carcinoma, Squamous Cell/metabolism*; Host-Pathogen Interactions; Metabolic Networks and Pathways; Case-Control Studies; Mass Spectrometry
From: International Journal of Oral Science 2025;17(1):1-1
CountryChina
Language:English
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.