Myoferlin; Mitochondria; DNA damage; p53; OXPHOS; metabolism
Résumé :
[en] Colon adenocarcinoma is the third most commonly diagnosed cancer and the second deadliest one. Metabolic reprogramming, described as an emerging hallmark of malignant cells, includes the predominant use of glycolysis to produce energy. Recent studies demonstrated that mitochondrial electron transport chain inhibitor reduced colon cancer tumour growth. Accumulating evidence show that myoferlin, a member of the ferlin family, is highly expressed in several cancer types, where it acts as a tumour-promoter and participates in the metabolic rewiring towards oxidative metabolism. In this study, we showed that myoferlin expression in colon cancer lesions is associated with low patient survival and is higher than in non-tumoural adjacent tissue. Human colon cancer cells silenced for myoferlin exhibit a reduced oxidative phosphorylation activity associated with mitochondrial fission leading, ROS accumulation, decreased cell growth, and increased apoptosis. We observed the triggering of a DNA damage response culminating to a cell cycle arrest in wild-type p53 cells. The use of a p53 null cell line or a compound able to restore p53 activity (Prima-1) reverted the effects induced by myoferlin silencing, confirming the involvement of p53. The recent identification of a compound interacting with a myoferlin C2 domain and bearing anti-cancer potency identifies, together with our demonstration, this protein as a suitable new therapeutic target in colon cancer.
Bellier, Justine ; Université de Liège - ULiège > Cancer-Metastases Research Laboratory
Herfs, Michael ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Peiffer, Raphaël ; Université de Liège - ULiège > Master sc. bioméd., à fin.
Agirman, Ferman ; Université de Liège - ULiège > Cancer-Metastases Research Laboratory
Maloujahmoum, Naïma ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Habraken, Yvette ; Université de Liège - ULiège > Molecular Biology of Diseases-Gene Expression & Cancer
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Bellahcene, Akeila ; Université de Liège - ULiège > Cancer-Metastases Research Laboratory
Castronovo, Vincenzo ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Peulen, Olivier ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
✱ Ces auteurs ont contribué de façon équivalente à la publication.
Langue du document :
Anglais
Titre :
Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis.
Date de publication/diffusion :
2019
Titre du périodique :
Oncogenesis
ISSN :
2157-9024
Maison d'édition :
Nature Publishing Group, Etats-Unis
Peer reviewed :
Peer reviewed vérifié par ORBi
Organisme subsidiant :
Fonds Léon Fredericq [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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