| Autor: |
Chepied A; Equipe 4CS, Laboratoire Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, Pôle Biologie Santé, University of Poitiers, 86073 Poitiers, France., Daoud-Omar Z; Equipe 4CS, Laboratoire Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, Pôle Biologie Santé, University of Poitiers, 86073 Poitiers, France., Meunier-Balandre AC; Equipe 4CS, Laboratoire Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, Pôle Biologie Santé, University of Poitiers, 86073 Poitiers, France., Laird DW; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada., Mesnil M; Equipe 4CS, Laboratoire Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, Pôle Biologie Santé, University of Poitiers, 86073 Poitiers, France., Defamie N; Equipe 4CS, Laboratoire Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, Pôle Biologie Santé, University of Poitiers, 86073 Poitiers, France. |
| Abstrakt: |
The resistance of glioblastomas to treatments is mainly the consequence of their invasive capacities. Therefore, in order to better treat these tumors, it is important to understand the molecular mechanisms which are responsible for this behavior. Previous work suggested that gap junction proteins, the connexins, facilitate the aggressive nature of glioma cells. Here, we show that one of them-connexin43 (Cx43)-is implicated in the formation and function of invadopodia responsible for invasion capacity of U251 human glioblastoma cells. Immunofluorescent approaches-combined with confocal analyses-revealed that Cx43 was detected in all the formation stages of invadopodia exhibiting proteolytic activity. Clearly, Cx43 appeared to be localized in invadopodia at low cell density and less associated with the establishment of gap junctions. Accordingly, lower extracellular matrix degradation correlated with less mature invadopodia and MMP2 activity when Cx43 expression was decreased by shRNA strategies. Moreover, the kinetics of invadopodia formation could be dependent on Cx43 dynamic interactions with partners including Src and cortactin. Interestingly, it also appeared that invadopodia formation and MMP2 activity are dependent on Cx43 hemichannel activity. In conclusion, these results reveal that Cx43 might be involved in the formation and function of the invadopodia of U251 glioblastoma cells. |
