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Mechanically Activated Channels in Glioma: the role of mechanoreceptor Piezo1 and hnRNP K in cancer as novel oncoregulators

Project description

Insight into the biology of glioblastoma

Glioblastoma multiforme (GBM) is a fast-growing tumour of the brain that is associated with poor prognosis and survival. GBM treatment options are limited, and tumours develop resistance to radiotherapy and chemotherapy, underscoring the importance of prompt diagnosis and new treatments. The scope of the EU-funded MAtChinG project is to provide fundamental insight into the biology and microenvironment of GBM. The work will focus on the master mechanoreceptor PIEZO1 and the crosstalk with the RNA-binding protein hnRNP K, known for its role in transcription, translation, and RNA stability. Researchers will investigate how PIEZO1 and hnRNP K may be associated with glioma stem cells and the onset and aggressiveness of GBM.

Objective

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.

Coordinator

FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III
Net EU contribution
€ 160 932,48
Address
C MELCHOR FERNANDEZ ALMAGRO 3
28029 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
Total cost
€ 160 932,48