Poster (Scientific congresses and symposiums)
Myoferlin, a new autophagy player in pancreatic cancer cells
Rademaker, Gilles; Hennequière, Vincent; Peixoto, Paul et al.
2017Giga-Day
 

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Keywords :
Myoferlin; Cancer; Pancreas; Autophagy
Abstract :
[en] Despite intensive research, Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the deadliest forms of cancer. Early-stage of the disease is clinically silent and the diagnosis of the disease is mostly made at an advanced stage. This late diagnosis contributes to one of the lowest 5-year survival rates (<5%). Today, PDAC are treated by surgery and/or adjuvant therapy, increasing only slightly the median survival of the patients. There is therefore an urgent need to develop new effective therapies for PDAC patients. PDAC are characterized by a high autophagic activity involved in its chemoresistance. Recently, key regulatory proteins controlling the metabolic reprogramming of PDAC cells were identified. By governing both autophagic flux and lysosomal catabolism, these proteins support the efficient processing of cargo from autophagy, providing PDAC cells with access to critical sources of nutrients. Interestingly, the high autophagy level in PDAC correlates with a poor patient outcome. Myoferlin, a member of the ferlin family overexpressed at protein level in different cancer types including PDAC, is a transmembrane protein able to bound to phospholipids and described to play an important function in membrane fusion. This characteristic invited us to investigate whether myoferlin could participate to autophagy, a process involving membrane fusion. Panc-1 cell line was used as a model of PDAC basal autophagy. Myoferlin expression was silenced using interfering RNA technology. Autophagosome abundance was evaluated by LC3-II western-blot and flow cytometry. Results indicated a significant increase in autophagosome abundance 48 h after myoferlin-silencing. This increase could arise from an increase of autophagy initiation or from an inhibition of autolysosome degradation. Using autophagy inhibitors, autophagic flux was evaluated by LC3-II and p62 western-blot after myoferlin-silencing. Results suggested a blockade in the autophagic process, impairing termination and autophagosome degradation by lysosome activity. Knowing the affinity of myoferlin for phospholipids, we wonder if this protein could interact with the phosphatidylethanolamine-conjugated LC3-II protein. Proximity-ligation assay suggested a close interaction between myoferlin and LC3. These results evoke an unexplored and undescribed role for myoferlin in autophagy. Understanding the involvement of myoferlin in this rediscovered biological process could give new clues in the development of new therapeutic strategy.
Research center :
Giga-Cancer - ULiège
Disciplines :
Oncology
Author, co-author :
Rademaker, Gilles  ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Hennequière, Vincent ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Peixoto, Paul;  Université de Bourgogne Franche-Comté > Laboratory of Biochemistry
Bellahcene, Akeila ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Castronovo, Vincenzo ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Peulen, Olivier  ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Myoferlin, a new autophagy player in pancreatic cancer cells
Publication date :
01 February 2017
Number of pages :
A0
Event name :
Giga-Day
Event place :
Liège, Belgium
Event date :
1er février 2017
Name of the research project :
Involvement of myoferlin in autophagy and metabolic adaptation in pancreas cancer
Funders :
ULiège - Université de Liège [BE]
Available on ORBi :
since 06 June 2017

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