Article (Scientific journals)
The gut microbial metabolite formate exacerbates colorectal cancer progression
TERNES, Dominik; TSENKOVA, Mina; POZDEEV, Vitaly et al.
2022In Nature Metabolism
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Keywords :
Gut microbiome; Colorectal cancer; Formate
Abstract :
[en] The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum, promotes CRC development. We describe molecular signatures linking CRC phenotypes with Fusobacterium abundance. Cocultures of F. nucleatum with patient-derived CRC cells display protumorigenic effects, along with a metabolic shift towards increased formate secretion and cancer glutamine metabolism. We further show that microbiome-derived formate drives CRC tumour invasion by triggering AhR signalling, while increasing cancer stemness. Finally, F. nucleatum or formate treatment in mice leads to increased tumour incidence or size, and Th17 cell expansion, which can favour proinflammatory profiles. Moving beyond observational studies, we identify formate as a gut-derived oncometabolite that is relevant for CRC progression.
Research center :
ULHPC - University of Luxembourg: High Performance Computing
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
TERNES, Dominik ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
TSENKOVA, Mina ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
POZDEEV, Vitaly ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
MEYERS, Marianne ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
KONCINA, Eric ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
ATATRI, Sura ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
SCHMITZ, Martine ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
KARTA, Jessica ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
SCHMOETTEN, Maryse ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Heinken, Almut;  School of Medicine, National University of Ireland, Galway, Ireland. ; Ryan Institute, National University of Galway, Galway, Ireland.
RODRIGUEZ, Fabien ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Delbrouck, Catherine;  Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg
GAIGNEAUX, Anthoula ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
GINOLHAC, Aurélien  ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Dan Nguyen, Tam Thuy;  Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Grandmougin, Lea;  Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Frachet-Bour, Audrey;  Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Martin-Gallausiaux, Camille;  Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
PIRES PACHECO, Maria Irene ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Neuberger-Castillo, Lorie;  Integrated BioBank of Luxembourg, Dudelange, Luxembourg
Miranda, Paulo;  National Center of Pathology, Laboratoire National de Santé, Dudelange, Luxembourg
Zuegel, Nikolaus;  Department of Surgery, Centre Hospitalier Emile Mayrisch, Esch-sur-Alzette, Luxembourg
Ferrand, Jean-Yves;  Clinical and Epidemiological Investigation Center, Department of Population Health, Luxembourg Institute of Health, Luxembourg, Luxembourg
Gantenbein, Manon;  Clinical and Epidemiological Investigation Center, Department of Population Health, Luxembourg Institute of Health, Luxembourg, Luxembourg
SAUTER, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Slade, Daniel Joseph;  Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
Thiele, Ines;  School of Medicine, National University of Ireland, Galway, Ireland ; Ryan Institute, National University of Galway, Galway, Ireland.
Meiser, Johannes;  Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg
HAAN, Serge  ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
WILMES, Paul ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology
LETELLIER, Elisabeth ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
More authors (21 more) Less
External co-authors :
yes
Language :
English
Title :
The gut microbial metabolite formate exacerbates colorectal cancer progression
Publication date :
04 April 2022
Journal title :
Nature Metabolism
eISSN :
2522-5812
Publisher :
Springer Nature, Berlin, Germany
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR11282028 - Role Of Mir-371-373 Cluster In Tumor Initiation And Metastatic Colonization, 2016 (15/03/2017-14/07/2020) - Elisabeth Letellier
Funders :
Fonds National de la Recherche - FnR, Fondation Cancer, Fondation du Pélican de Mie and Pierre Hippert-Faber
Available on ORBilu :
since 01 September 2022

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