Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis.

Rademaker, Gilles; Costanza, Brunella; Bellier, Justine; Herfs, Michael; Peiffer, Raphaël; Agirman, Ferman; Maloujahmoum, Naïma; Habraken, Yvette; Delvenne, Philippe; Bellahcene, Akeila; Castronovo, Vincenzo; Peulen, Olivier

doi:10.1038/s41389-019-0130-6

Article (Scientific journals)

Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis.

Rademaker, Gilles; Costanza, Brunella; Bellier, Justine et al.

2019 • In Oncogenesis

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/233017

DOI
10.1038/s41389-019-0130-6

PubMed
30850580

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Keywords :

Myoferlin; Mitochondria; DNA damage; p53; OXPHOS; metabolism

Abstract :

[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.

Research center :

Giga-Cancer - ULiège

Disciplines :

Oncology
Biochemistry, biophysics & molecular biology

Author, co-author :

Rademaker, Gilles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire

Costanza, Brunella

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

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis.

Publication date :

2019

Journal title :

Oncogenesis

ISSN :

2157-9024

Publisher :

Nature Publishing Group, United States

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

Fonds Léon Fredericq [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]

Available on ORBi :

since 18 February 2019

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