Article (Scientific journals)
Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells
Rademaker, Gilles; Boumahd, Yasmine; Peiffer, Raphaël et al.
2022In Redox Biology, 53, p. 102324
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Keywords :
Pancreas cancer; ferroptosis; mitophagy; myoferlin; iron
Abstract :
[en] Myoferlin, an emerging oncoprotein, has been associated with a low survival in several cancer types including pancreas ductal adenocarcinoma where it controls mitochondria structure and respiratory functions. Owing to the high susceptibility of KRAS-mutated cancer cells to iron-dependent cell death, ferroptosis, and to the high iron content in mitochondria, we investigated the relation existing between mitochondrial integrity and iron-dependent cell death. We discovered that myoferlin targeting with WJ460 pharmacological compound triggered mitophagy and ROS accumulation culminating with lipid peroxidation and apoptosis-independent cell death. WJ460 caused a reduction of the abundance of ferroptosis core regulators xc- cystine/glutamate transporter and GPX-4. Mitophagy inhibitor Mdivi1 and iron chelators inhibited the myoferlin-related ROS production and restored cell growth. Additionally, we reported a synergic effect between ferroptosis inducers, erastin and RSL3, and WJ460.
Research center :
GIGA-LRM - GIGA Cancer-Metastases Research Laboratory - ULiège
d‐BRU - Dental Biomaterials Research Unit - ULiège [BE]
Disciplines :
Oncology
Author, co-author :
Rademaker, Gilles   ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Boumahd, Yasmine  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Peiffer, Raphaël  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Anania, Sandy  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Wissocq, Tom ;  Université de Liège - ULiège > Faculté de Médecine > Doct. sc. bioméd. & pharma. (paysage) ; Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Liégeois, Maude ;  Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Biochimie et biologie moléculaire
Luis, Géraldine ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
Sounni, Nor Eddine  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
Agirman, Ferman ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Maloujahmoum, Naïma ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
De Tullio, Pascal ;  Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Thiry, Marc  ;  Université de Liège - ULiège > Département des sciences de la vie > Biologie cellulaire
Bellahcene, Akeila ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Castronovo, Vincenzo ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Peulen, Olivier  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
More authors (5 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells
Publication date :
July 2022
Journal title :
Redox Biology
eISSN :
2213-2317
Publisher :
Elsevier, Netherlands
Volume :
53
Pages :
102324
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 April 2022

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