CONTRIBUTION OF THE HYPOXIA-ODZ1 AXIS TO THE INVASIVE CAPACITY OF GLIOBLASTOMA (Q3138921): Difference between revisions
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(Created claim: summary (P836): The low survival of glioblastoma (GBM) patients has been attributed to their genetic heterogeneity and tumor microenvironment factors such as hypoxia and aberrant signs of growth factors. One of the most prominent features of the GBM is its high infiltrating capacity, which adds great complexity to the clinical management of patients. Recently, we described that the transmembranal protein ODZ1, induces an invasive mesenchymal phenotype in GBM ce...) |
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CONTRIBUTION OF THE HYPOXIA-ODZ1 AXIS TO THE INVASIVE CAPACITY OF GLIOBLASTOMA | |||
Revision as of 13:20, 12 October 2021
Project Q3138921 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | CONTRIBUTION OF THE HYPOXIA-ODZ1 AXIS TO THE INVASIVE CAPACITY OF GLIOBLASTOMA |
Project Q3138921 in Spain |
Statements
36,000.0 Euro
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72,000.0 Euro
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50.0 percent
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1 January 2018
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31 March 2021
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FUNDACION INSTITUTO DE INVESTIGACION MARQUES DE VALDECILLA (IDIVAL)
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43°27'43.34"N, 3°48'35.89"W
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39075
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La baja supervivencia de los pacientes con glioblastoma (GBM) se ha atribuido a su heterogeneidad genética y a factores del microambiente tumoral tales como la hipoxia y las señales aberrantes de factores de crecimiento. Una de las características más destacadas del GBM es su elevada capacidad infiltrante, que añade una gran complejidad al manejo clínico de los pacientes. Recientemente, describimos que la proteína transmembranal ODZ1, induce un fenotipo mesenquimal invasivo en las células de GBM activando la ruta transcripcional Myc-RhoA. Por otro lado, la hipoxia es clave en la invasión tumoral y se asocia a la activación de Myc, entre otros factores, y al fenotipo mesenquimal en GBM. Pese a su relevancia, no se conocen marcadores específicos de hipoxia. Cabe añadir que la hipoxia promueve cambios epigenéticos por metilación del DNA y que nuestros datos preliminares relacionan la expresión de ODZ1 con procesos de isquemia/hipoxia cerebral. En base a esto, nos proponemos estudiar la contribución de ODZ1 en el proceso invasivo del GBM y su relación con la hipoxia. Para ello utilizaremos modelos in vitro e in vivo de GBM y analizaremos imágenes de RMN y biopsias de pacientes. Pretendemos, en definitiva, aportar evidencias sobre el valor pronóstico de ODZ1 y de un posible marcador específico de hipoxia (firma epigenética) en GBM y determinar si ODZ1 es un mediador del efecto invasivo de la hipoxia. (Spanish)
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The low survival of glioblastoma (GBM) patients has been attributed to their genetic heterogeneity and tumor microenvironment factors such as hypoxia and aberrant signs of growth factors. One of the most prominent features of the GBM is its high infiltrating capacity, which adds great complexity to the clinical management of patients. Recently, we described that the transmembranal protein ODZ1, induces an invasive mesenchymal phenotype in GBM cells by activating the Myc-RhoA transcriptional pathway. On the other hand, hypoxia is key in tumor invasion and is associated with the activation of Myc, among other factors, and the mesenchymal phenotype in GBM. Despite their relevance, no specific markers of hypoxia are known. It should be added that hypoxia promotes epigenetic changes by DNA methylation and that our preliminary data relate the expression of ODZ1 to processes of cerebral ischemia/hypoxia. Based on this, we intend to study the contribution of ODZ1 to the invasive process of the BBM and its relationship with hypoxia. For this we will use in vitro and in vivo models of GBM and analyse images of MRI and biopsies of patients. In short, we intend to provide evidence on the prognostic value of ODZ1 and a possible specific marker of hypoxia (epigenetic signature) in GBM and to determine whether ODZ1 is a mediator of the invasive effect of hypoxia. (English)
12 October 2021
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Santander
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Identifiers
PI17_01399
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