Comunicación

A POSSIBLE KEY TARGET FOR BLOCKING GLIOBLASTOMA PROGRESSION: CHAPERONE-MEDIATED AUTOPHAGY IN PERICYTES

Autores:

María Luisa Molina Gallego1, María Botía2, PEDRO APARICIO ALONSO3, Ana María Cuervo4, Fernando Macián5, Salvador Martínez Pérez6, Rut VALDOR ALONSO7

Afiliaciones:

(1) AUTOFAGIA, INMUNIDAD Y CÁNCER, IMIB-Arrixaca, España
(2) [GI/IMIB/C041/2011] REGIONALIZACION CEREBRAL Y GENES DEL DESARROLLO, IMIB-Arrixaca, España, 03185, España (Comunidad Valenciana), España (Región de Murcia)
(3) CIRUGÍA DIGESTIVA, ENDOCRINA Y TRASPLANTE DE ÓRGANOS ABDOMINALES, IMIB-Arrixaca, España
(4) Department of Developmental Molecular Biology at Albert Einstein College of Medicine, Institute for Aging Studies,  Bronx, NY, 10461, Estados Unidos
(5) Department of Pathology at Albert Einstein College of Medicine, Institute for Aging Studies,  Bronx, NY, 10461, Estados Unidos
(6) Instituto de Neurociencias UMH-CSIC, CIBERSAM of ISCIII, 03550 San Juan de Alicante, Spain, España (Región de Murcia)
(7) REGIONALIZACION CEREBRAL Y GENES DEL DESARROLLO, IMIB-Arrixaca, España

Comunicación:

Antecedentes:

The lack of knowledge of the pathogenesis and the progression mechanisms of Glioblastoma (GB), the most aggressive brain tumor, contributes to none successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function during GB progression. GB-induced CMA in PC is necessary for proteostasis that promotes interaction with GB and, therefore, for an immunosuppressive function that facilitates tumor progression. Objective: to provide knowledge about the regulation and functional consequences of GB-induced CMA in PC.

Métodos:

Methods: studies of RNA-seq have been done in GB-conditioned pericytes with and without CMA compared to control pericytes after 72 hours of co-culture.

Resultados:

Results: We have found several gene expression pathways differentially enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Our data show that the phagosome formation, cell senescence, focal adhesion and the effector function to promote anti-tumor immune responses are the most affected pathways, reveling some transcription factors, as positive regulators of these processes that might be degraded by GB-induced CMA in pericytes, leading to facilitate GB progression.

Conclusiones:

Conclusion: our results identify gene expression signaling pathways and possible new molecular markers that drive to the consequences of an aberrant upregulation of GB-induced CMA in PC and therefore, lead to "permissive" immune niche in the progression of GB.


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Dirección

Campus de Ciencias de la Salud
Carretera Buenavista s/n, 30120 El Palmar
Murcia, España

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