Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells

[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/Unit :

GIGA-LRM - GIGA Cancer-Metastases Research Laboratory - ULiège
d‐BRU - Dental Biomaterials Research Unit - ULiège

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

More authors (5 more)

^✱ 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 :

Pages :

102324

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://doi.org/10.1016/j.redox.2022.102324

Available on ORBi :

since 25 April 2022

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