Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer
Abstract In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phospho...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-41951-3 |
| _version_ | 1827723548602400768 |
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| author | Ewa Pasquereau-Kotula Giulia Nigro Florent Dingli Damarys Loew Patrick Poullet Yi Xu Scott Kopetz Jennifer Davis Lucie Peduto Catherine Robbe-Masselot Philippe Sansonetti Patrick Trieu-Cuot Shaynoor Dramsi |
| author_facet | Ewa Pasquereau-Kotula Giulia Nigro Florent Dingli Damarys Loew Patrick Poullet Yi Xu Scott Kopetz Jennifer Davis Lucie Peduto Catherine Robbe-Masselot Philippe Sansonetti Patrick Trieu-Cuot Shaynoor Dramsi |
| author_sort | Ewa Pasquereau-Kotula |
| collection | DOAJ |
| description | Abstract In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of several cancer hallmark pathways such as MAPK, mTOR and integrin/ILK/actin, affecting epithelial and stromal colonic cells. Importantly, an independent analysis of protein arrays of human colon tumors colonized with SGG showed up-regulation of PI3K/Akt/mTOR and MAPK pathways, providing clinical relevance to our findings. To test SGG’s capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grew ex vivo organoids which revealed unusual structures with compact morphology. Taken together, our results demonstrate the oncogenic role of SGG UCN34 in a murine model of CRC associated with activation of multiple cancer-related signaling pathways. |
| first_indexed | 2024-03-10T22:02:19Z |
| format | Article |
| id | doaj.art-5d45b4747a824fb6846164ba6cf8c845 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T22:02:19Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5d45b4747a824fb6846164ba6cf8c8452023-11-19T12:54:45ZengNature PortfolioScientific Reports2045-23222023-09-0113111510.1038/s41598-023-41951-3Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancerEwa Pasquereau-Kotula0Giulia Nigro1Florent Dingli2Damarys Loew3Patrick Poullet4Yi Xu5Scott Kopetz6Jennifer Davis7Lucie Peduto8Catherine Robbe-Masselot9Philippe Sansonetti10Patrick Trieu-Cuot11Shaynoor Dramsi12Biology of Gram-Positive Pathogens Unit, Institut Pasteur, Université Paris Cité, CNRS UMR6047Stroma, Inflammation and Tissue Repair Unit, Institut Pasteur, Université Paris Cité, INSERM U1224Institut Curie, PSL Research University, CurieCoreTech Spectrométrie de Masse ProtéomiqueInstitut Curie, PSL Research University, CurieCoreTech Spectrométrie de Masse ProtéomiqueInstitut Curie, Bioinformatics Core Facility (CUBIC), INSERM U900, PSL Research University, Mines Paris TechCenter for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterStroma, Inflammation and Tissue Repair Unit, Institut Pasteur, Université Paris Cité, INSERM U1224Université de Lille, CNRS, UMR8576-UGSF-Unité de Glycobiologie Structurale et FonctionnelleInstitut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, and College de FranceBiology of Gram-Positive Pathogens Unit, Institut Pasteur, Université Paris Cité, CNRS UMR6047Biology of Gram-Positive Pathogens Unit, Institut Pasteur, Université Paris Cité, CNRS UMR6047Abstract In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of several cancer hallmark pathways such as MAPK, mTOR and integrin/ILK/actin, affecting epithelial and stromal colonic cells. Importantly, an independent analysis of protein arrays of human colon tumors colonized with SGG showed up-regulation of PI3K/Akt/mTOR and MAPK pathways, providing clinical relevance to our findings. To test SGG’s capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grew ex vivo organoids which revealed unusual structures with compact morphology. Taken together, our results demonstrate the oncogenic role of SGG UCN34 in a murine model of CRC associated with activation of multiple cancer-related signaling pathways.https://doi.org/10.1038/s41598-023-41951-3 |
| spellingShingle | Ewa Pasquereau-Kotula Giulia Nigro Florent Dingli Damarys Loew Patrick Poullet Yi Xu Scott Kopetz Jennifer Davis Lucie Peduto Catherine Robbe-Masselot Philippe Sansonetti Patrick Trieu-Cuot Shaynoor Dramsi Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer Scientific Reports |
| title | Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer |
| title_full | Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer |
| title_fullStr | Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer |
| title_full_unstemmed | Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer |
| title_short | Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer |
| title_sort | global proteomic identifies multiple cancer related signaling pathways altered by a gut pathobiont associated with colorectal cancer |
| url | https://doi.org/10.1038/s41598-023-41951-3 |
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