[en] The role of phosphatidylcholine transporters such as Stard7 in intestinal cancer development is unknown. To explore this issue, we generated a mouse model lacking Stard7 in intestinal epithelial cells (IECs). Loss of Stard7 impaired mitochondrial Complex I activity, led to a severe metabolic and lipid reprogramming, enhanced mitochondrial ROS production and potentiated an mTORC1/ATF4 signature. As a result, levels of enzymes involved in serine biosynthesis were enhanced in Stard7-deficient IECs. We next assessed the consequences of Stard7 deficiency in both Wnt-dependent tumor initiation and in inflammation-driven tumor development. Strikingly, despite generating similar molecular signatures, Stard7 deficiency inhibited tumor development in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice but promoted Wnt-driven cancer initiation in the intestine. Apc+/Min mice lacking Stard7 in IECs developed more tumors in the distal colon as well as a specific microbiota signature. Collectively, our results suggest that the genetic status critically controls the effects of Stard7 deficiency on intestinal tumor development.
Disciplines :
Oncology
Author, co-author :
Shostak, Kateryna ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Chen, Yu ; Université de Liège - ULiège > Département de pharmacie
Maurizy, Chloé ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Rademaker, Gilles ; Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Xu, Xinyi; Laboratory of Cancer Biology, GIGA Cancer, University of Liege, Sart-Tilman, Liège, Belgium
Blomme, Arnaud ; Université de Liège - ULiège > Département de pharmacie
Close, Pierre ; Université de Liège - ULiège > Département de pharmacie ; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WEL Research Institute, WELBIO Department, Wavre, Belgium
Renson, Olivier ; GIGA Genomics Platform, University of Liege, Liege, Belgium
Van Hul, Matthias; Metabolism and Nutrition Research group, Louvain Drug Research Institute (LDRI) and Institute of Experimental and Clinical Research (IREC), UCLouvain, Université catholique de Louvain, Brussels, Belgium
Cani, Patrice D ; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WEL Research Institute, WELBIO Department, Wavre, Belgium ; Metabolism and Nutrition Research group, Louvain Drug Research Institute (LDRI) and Institute of Experimental and Clinical Research (IREC), UCLouvain, Université catholique de Louvain, Brussels, Belgium ; Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
Klein, Sebastian; Institute for Pathology-University Hospital of Cologne, Cologne, Germany ; Department of Hematology and Stem Cell Transplantation, University Duisburg-Essen, University Hospital Essen, Essen, Germany
Florin, Alexandra; Institute for Pathology-University Hospital of Cologne, Cologne, Germany
Büttner, Reinhard ; Institute for Pathology-University Hospital of Cologne, Cologne, Germany
Cataldo, Didier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et pathologiques
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Nemazanyy, Ivan ; Platform for Metabolic Analyses, Structure Fédérative de Recherche Necker, INSERM US24/CNRS UMS 3633, Paris, France
WATHIEU, Caroline ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Hego, Alexandre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
WELBIO - Walloon Excellence in Life Sciences and Biotechnology Belgian Foundation against Cancer ULiège - University of Liège EOS - The Excellence Of Science Program F.R.S.-FNRS - Fonds de la Recherche Scientifique UCL - Catholic University of Louvain
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