References of "Castronovo, Vincenzo"
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See detailMyoferlin is a yet unknown interactor of the mitochondrial dynamics’ machinery in pancreas cancer cells
Anania, Sandy ULiege; Peiffer, Raphaël ULiege; Rademaker, Gilles ULiege et al

in Cancers (2020), 12(6), 1643

Pancreas ductal adenocarcinoma is one of the deadliest cancers where surgery remains the main survival factor. Mitochondria were described to be involved in tumor aggressiveness in several cancer types ... [more ▼]

Pancreas ductal adenocarcinoma is one of the deadliest cancers where surgery remains the main survival factor. Mitochondria were described to be involved in tumor aggressiveness in several cancer types including pancreas cancer. We have previously reported that myoferlin controls mitochondrial structure and function, and demonstrated that myoferlin depletion disturbs the mitochondrial dynamics culminating to a mitochondrial fission. In order to unravel the mechanism underlying this observation, we explored the myoferlin localization in pancreatic cancer cells and showed a colocalization with the mitochondrial dynamic machinery element: mitofusin. This colocalization was confirmed in several pancreas cancer cell lines and in normal cell lines as well. Moreover, in pancreas cancer cell lines, it appeared that myoferlin interacted with mitofusin. These discoveries open-up new research avenue aiming at modulating mitofusin function in pancreas cancer. [less ▲]

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See detailImportance des acides gras polyinsaturés oméga-3 durant la grossesse: mode ou réalité scientifique?
Hoge, Axelle ULiege; Nisolle, Michelle ULiege; Guillaume, Michèle ULiege et al

in Gunaïkeia. Société Royale Belge de Gynécologie et d'Obstétrique (2020), 25(2),

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See detailMethylglyoxal stress contributes to immunosuppression in breast cancer
Wissocq, Tom ULiege; Hubert, Pascale ULiege; Caprasse, Maurine ULiege et al

Poster (2020, February 07)

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See detailMethylglyoxal Scavengers Resensitize KRAS-Mutated Colorectal Tumors to Cetuximab
Bellier, Justine ULiege; Nokin, Marie-Julie ULiege; Caprasse, Maurine ULiege et al

in Cell Reports (2020), 30(5), 1400-14166

The use of cetuximab anti-epidermal growth factor receptor (anti-EGFR) antibodies has opened the era of targeted and personalized therapy in colorectal cancer (CRC). Poor response rates have been ... [more ▼]

The use of cetuximab anti-epidermal growth factor receptor (anti-EGFR) antibodies has opened the era of targeted and personalized therapy in colorectal cancer (CRC). Poor response rates have been unequivocally shown in mutant KRAS and are even observed in a majority of wild-type KRAS tumors. Therefore, patient selection based on mutational profiling remains problematic. We previously identified methylglyoxal (MGO), a by-product of glycolysis, as a metabolite promoting tumor growth and metastasis. Mutant KRAS cells under MGO stress show AKT-dependent survival when compared with wild-type KRAS isogenic CRC cells. MGO induces AKT activation through phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin 2 (mTORC2) and Hsp27 regulation. Importantly, the sole induction of MGO stress in sensitive wild-type KRAS cells renders them resistant to cetuximab. MGO scavengers inhibit AKT and resensitize KRAS-mutated CRC cells to cetuximab in vivo. This study establishes a link between MGO and AKT activation and pinpoints this oncometabolite as a potential target to tackle EGFR-targeted therapy resistance in CRC. [less ▲]

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See detailRole of myoferlin in mitochondrial dynamics and metabolic fitness of Pancreatic Ductal Adenocarcinoma
Anania, Sandy ULiege; Rademaker, Gilles ULiege; Bellahcene, Akeila ULiege et al

Poster (2019, December)

Pancreatic cancer is the 7th most common cause of cancer mortality in the world. It is predicted to become the 2nd leading cause of cancer-related death in 2030. In the majority of cases, due to a late ... [more ▼]

Pancreatic cancer is the 7th most common cause of cancer mortality in the world. It is predicted to become the 2nd leading cause of cancer-related death in 2030. In the majority of cases, due to a late diagnosis, the tumor is not resectable and already disseminated. Therefore, new specific biomarkers providing early diagnosis for pancreatic cancer are needed. In addition to the lack of specific and early biomarkers, chemotherapies (gemcitabine and folfirinox) poorly improve the overall survival of Pancreatic Ductal Adenocarcinoma (PDAC) patients. Hence, a better understanding of physiopathological processes underlying PDAC is required in order to offer more effective treatments. Myoferlin is a 230 kDa protein with multiple C2 domains known to interact, through calcium binding, with negatively charged phospholipids. This protein was first described in myoblast fusion. Interestingly, Myoferlin is also overexpressed in several cancers, including pancreatic cancer, where it plays a role in endocytosis, exocytosis, and has been located in exosomes. Recently, our team showed a fragmentation of the mitochondrial network in PDAC cells when myoferlin was depleted using siRNA. Understanding the mechanism underlying this mitochondrial disruption would be of great interest as mitochondria are major actors in cancer development, progression and resistance. Owing to the known role of myoferlin in membrane fusion, we assessed its direct involvement in the mitochondrial fusion machinery. Indeed, if myoferlin is a part of the mitochondrial fusion machinery, its silencing together with an unopposed fission would lead to mitochondrial fragmentation. First, we performed immunofluorescence to colocalize myoferlin and a mitochondrial outer membrane 65kDa protein. Colocalization studies showed no significant colocalization. We then performed immunofluorescence to stained myoferlin and the main factor of mitochondrial fusion mitofusin-1/2 (MFN1/2). Colocalization image analysis revealed a 60% colocalization between both proteins. Those results were further confirmed by PLA (Proximity Ligation Assay). Finally, to evaluate a direct protein-protein interaction, we performed a co-immunoprecipitation assay. The main isoform of myoferlin appeared to coimmunoprecipitate with MFN1/2, suggesting a direct interaction between these proteins. [less ▲]

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See detailRole of myoferlin in mitochondrial dynamics and metabolic fitness of PDAC
Anania, Sandy ULiege; Rademaker, Gilles ULiege; Wissocq, Tom ULiege et al

Poster (2019, October)

Our data strongly suggest that myoferlin interacts with MFN. Indeed, if myoferlin is a part of the mitochondrial fusion machinery, its silencing together with an unopposed fission would lead to ... [more ▼]

Our data strongly suggest that myoferlin interacts with MFN. Indeed, if myoferlin is a part of the mitochondrial fusion machinery, its silencing together with an unopposed fission would lead to mitochondrial fragmentation. [less ▲]

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See detailRole of myoferlin in mitochondrial dynamics and metabolic fitness of pancreas cancer
Anania, Sandy ULiege; Rademaker, Gilles ULiege; Wissocq, Tom ULiege et al

Poster (2019, September 06)

Pancreatic cancer is the 7th most common cause of cancer mortality in the world. It is predicted to become the second leading cause of cancer-related death in 2030. Myoferlin is a 230 kDa protein ... [more ▼]

Pancreatic cancer is the 7th most common cause of cancer mortality in the world. It is predicted to become the second leading cause of cancer-related death in 2030. Myoferlin is a 230 kDa protein overexpressed in pancreatic cancer. Recently, our team showed a fragmentation of the mitochondrial network in PDAC cells when myoferlin was depleted using siRNA. Understanding the mechanism underlying this mitochondrial disruption would be of great interest as mitochondria are major actors in cancer development, progression and resistance [less ▲]

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See detailFerlin overview: from membrane to cancer biology
Peulen, Olivier ULiege; Rademaker, Gilles ULiege; Anania, Sandy ULiege et al

in Cells (2019), 8

In mammal myocytes, endothelial cells, and inner ear cells, ferlins are proteins involved in membrane processes such as fusion, recycling, endo- and exocytosis. They harbour several C2 domains allowing ... [more ▼]

In mammal myocytes, endothelial cells, and inner ear cells, ferlins are proteins involved in membrane processes such as fusion, recycling, endo- and exocytosis. They harbour several C2 domains allowing their interaction with phospholipids. Membrane biology is of extreme importance for cell survival and signalling, making Ferlin proteins core machinery indispensable for cancer cell adaptation to hostile environment. Expression of several Ferlin genes was described as altered in several cancer types. Among them myoferlin was recently discovered as highly expressed in several tumoural tissues, and negatively correlated to patient survival. Evidences suggest that myoferlin, when overexpressed, enhances cancer cell proliferation, migration and metabolism by affecting various aspects of membrane biology. Targeting myoferlin using pharmacological compounds, gene transfer technology, or interfering RNA is now considered as an emerging therapeutic strategy. [less ▲]

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See detailMyoferlin contributes to the metastatic phenotype of pancreatic cancer cells by enhancing their migratory capacity through the control of oxidative phosphorylation
Rademaker, Gilles ULiege; Costanza, Brunella ULiege; Anania, Sandy ULiege et al

in Cancers (2019), 11(6),

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 ... [more ▼]

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. [less ▲]

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See detailNon-destructive sampling device for extraction of a marker
Castronovo, Vincenzo ULiege; Emmerechts, Carl

Patent (2019)

Method and device for extraction of markers, comprising: introducing a sample into a removable support basket placed in the housing of a cell of an extraction device provided with a flexible membrane and ... [more ▼]

Method and device for extraction of markers, comprising: introducing a sample into a removable support basket placed in the housing of a cell of an extraction device provided with a flexible membrane and immersing the tissue sample in a liquid previously introduced into the housing, followed by hermetic closing of the extraction cell and application of a pressure cycle on the flexible membrane for a period of 1 to 5 minutes at a frequency between 1 and 2 Hz. Then, total or partial recovery of the liquid immersing the sample after the pressure cycle and detection of the markers present in the liquid. [less ▲]

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