Description du projet
Un aperçu de la biologie du glioblastome
Le glioblastome multiforme (GBM) est une tumeur cérébrale à croissance rapide associée à un pronostic défavorable et à une survie réduite. Les options de traitement du GBM sont limitées et les tumeurs développent une résistance à la radiothérapie et à la chimiothérapie, ce qui met en exergue l’importance d’un diagnostic précoce et de nouveaux traitements. Le projet MAtChinG, financé par l’UE, entend fournir des informations fondamentales sur la biologie et le microenvironnement des GBM. Les travaux seront axés sur le mécanorécepteur PIEZO1 et les interactions entre la protéine de liaison à l’ARN hnRNP K, connue pour son rôle dans la transcription, la traduction et la stabilité de l’ARN. Les chercheurs se pencheront sur la manière dont PIEZO1 et hnRNP K peuvent être associés aux cellules souches des gliomes et à l’apparition et à l’agressivité des GBM.
Objectif
Glioblastoma multiforme (GBM) is one of the most common and aggressive forms of brain tumour, affecting 2-3 per 100,000 adults per year, and with a usual survival time of 14-18 months after diagnosis with only a 10% of the patients living up to 5 years after it. Because of its location, early detection of the tumour and surgical removal may be complicated. Furthermore, its fast growth rate and migration capacity makes it extremely aggressive. Aditionally the presence of glioma cancer stem cells contribute to radio- and chemioresistance of GBM. Because of all this, a deeper understanding about its genetical, biochemical and microenviromental nature is needed. In order to gain more insight into the formation and development of glioma, in this proposed project we hypothesize that the heterogeneous nuclear ribonucleoprotein K (hnRNPK) and the mechanically activated ion channel Piezo1 constitute an axis that promotes the onset and progression of glioma. HnRNPK is a multifunctional protein that influences transcription, translation and RNA stability amongst other function, and it exerts its function depending on its phosphorylation state, which is modulated by kinases such as ERK, JNK or PKC. Piezo1 is a stretch-activated cation channel, that activated upon mechanical cues allowing the influx of calcium in the cell and activation of multiple cascades, such as ERK or PKC pathways, as well as in apoptosis and migration. Both hnRNPK and Piezo1 are upregulated in gliomas and preliminary data suggests a relation in their regulation. Here, we proposed that there is a regulation between Piezo1 and hnRNPK, and that this axis promotes the onset of gliomas cancer stem cells and contributes to its aggressiveness. With this project, we aim to investigate how this axis could contribute to the formation and aggressiveness of gliomas, and how its modulation can contribute to its control, therefore turning Piezo1 and hnRNPK into a new promising target for glioma treatment.
Champ scientifique
- natural scienceschemical sciencesinorganic chemistryalkaline earth metals
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticsRNA
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
28029 Madrid
Espagne