Fiche publication
Date publication
mars 2015
Journal
Histochemistry and cell biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DUCA Laurent
,
Pr PLOTON Dominique
,
Dr TERRYN Christine
Tous les auteurs :
Chatron-Colliet A, Lalun N, Terryn C, Kurdykowski S, Lorenzato M, Rusciani A, Ploton D, Duca L, Bobichon H
Lien Pubmed
Résumé
During melanoma tumour growth, cancerous cells are exposed to the immediate surrounding the micro- and macro environment, which is largely modified through the degradation of the extracellular matrix by fibroblast-derived metalloproteinases. Among the degradation products, (VGVAPG)3, an elastin peptide is known to stimulate the proliferation of both fibroblasts and cancerous cells by binding to the elastin-binding receptor and activating the MEK/ERK signal transduction pathway. As this process strongly modifies mRNA synthesis, we investigated its effect on the relative three-dimensional organisation of the major partners of the mRNA splicing machinery: promyelocytic nuclear bodies (PML-NBs ) and splicing component 35 speckles (SC35) of normal fibroblasts and melanoma SK-MEL-28 cells. SC35 and PML-NBs proteins were immunolabeled and imaged by confocal microscopy within these cells cultured with (VGVAPG)3. Three-dimensional reconstruction was performed to elucidate the organisation of PML-NBs and SC35 speckles and their spatial relationship. In G0 cells, SC35 speckles were sequestered in PML-NBs. Shortly after (VGVAPG)3 stimulation, the three-dimensional organisation of PML-NBs and SC35 speckles changed markedly. In particular, SC35 speckles gradually enlarged and adopted a heterogeneous organisation, intermingled with PML-NBs. Conversely, inhibition of the elastin-binding protein or MEK/ERK pathway induced a remarkable early sequestration of condensed SC35 speckles in PML-NBs, the hallmark of splicing inhibition. The 3D architecture of speckles/PML-NBs highlights the modulation in their spatial relationship, the multiple roles of PML-NBs in activation, inhibition and sequestration, and provides the first demonstration of the dependence of PML-NBs and SC35 speckles on the elastin peptide for these functions.
Mots clés
Adult, Cell Line, Cell Nucleus, drug effects, Cell Proliferation, drug effects, Elastin, chemistry, Fibroblasts, cytology, Humans, Imaging, Three-Dimensional, Melanoma, pathology, Oligopeptides, pharmacology, RNA Splicing, drug effects, Structure-Activity Relationship
Référence
Histochem. Cell Biol.. 2015 Mar;143(3):245-58
