title: The proapoptotic C16-ceramide-dependent pathway requires the death-promoting factor Btf in colon adenocarcinoma cells.
abstract: Ceramides are central molecules in sphingolipid metabolism. They are involved in the regulation of cancer-cell growth, differentiation, senescence and apoptosis. To better understand how these secondary messengers induce their biological effects, adenocarcinoma cells (HCT116) were treated with exogenous long-chain ceramides (C16-ceramide) in order to mimic endogenous sphingolipids. This treatment induced a decrease of cell viability partly due to apoptosis as shown by PARP cleavage and a decrease of pro-caspase 3. Two-dimensional differential in-gel electrophoresis (2D-DIGE) revealed the differential expression of 51 proteins in response to C16-ceramide. These proteins are notably involved in cell proliferation, apoptosis, protein transport and transcriptional regulation. Among them, the cell death-promoting factor Btf was found to be implicated in the apoptotic signal triggered by ceramide. In adenocarcinoma cells, Btf regulates apoptosis related proteins such as Mdm2, p53, BAX and pBcl-2 and thus plays an important role in the ceramide mediated cell death. These findings bring new insight into the proapoptotic ceramide-dependent signaling pathway.
authors.affiliation: GIGA Signal Transduction, Unit of Medical Chemistry, University of Liège, Sart-Tilman, Belgium.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Rénert
authors.forename: Pierre
authors.initials: P
authors.lastname: Leprince
authors.forename: Marc
authors.initials: M
authors.lastname: Dieu
authors.forename: Jenny
authors.initials: J
authors.lastname: Renaut
authors.forename: Martine
authors.initials: M
authors.lastname: Raes
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chapelle
authors.forename: Jacques
authors.initials: J
authors.lastname: Piette
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Merville
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival; D002518:Ceramides / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D045325:HCT116 Cells; D006801:Humans; D020543:Proteome / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C119386:BCLAF1 protein, human; D002518:Ceramides; D020543:Proteome; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; C097760:N-palmitoylsphingosine; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2