Myoferlin contributes to the metastatic phenotype of pancreatic cancer cells by enhancing their migratory capacity through the control of oxidative phosphorylation
[en] Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies with an overall survival of 5%, and is the second cause of death by cancer, mainly linked to its high metastatic aggressiveness. Accordingly, understanding the mechanisms sustaining the PDAC metastatic phenotype remains a priority. In this study, we have generated and used a murine in vivo model to select clones from the human PANC-1 PDAC cell line that exhibit a high propensity to seed and metastasized into the liver. We showed that myoferlin, a protein previously reported to be overexpressed in PDAC, is significantly involved in the migratory abilities of the selected cells. We first report that highly PANC-1 metastatic clones expressed significantly higher myoferlin level than the corresponding low metastatic ones. Using scratch wound and Boyden’s chamber assays, we show that cells expressing high myoferlin level have higher migratory potential than cells characterized by a low myoferlin abundance. Moreover, we demonstrate that myoferlin silencing leads to a migration decrease associated to a reduction of mitochondrial respiration. Since mitochondrial oxidative phosphorylation has been shown to be implicated in the tumor progression and dissemination, our data identify myoferlin as a valid potential therapeutic target in PDAC.
Research center :
Giga-Cancer - ULiège d‐BRU - Dental Biomaterials Research Unit - ULiège [BE]
Disciplines :
Oncology
Author, co-author :
Rademaker, Gilles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Costanza, Brunella ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Anania, Sandy ; Université de Liège - ULiège > Cancer-Metastases Research Laboratory
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
Di Valentin, Emmanuel ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
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
Language :
English
Title :
Myoferlin contributes to the metastatic phenotype of pancreatic cancer cells by enhancing their migratory capacity through the control of oxidative phosphorylation
Publication date :
June 2019
Journal title :
Cancers
eISSN :
2072-6694
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
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