The unfolded protein response machinery in glioblastoma genesis, chemoresistance and as a druggable target.
CNS Neurosci Ther
; 30(7): e14839, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-39021040
ABSTRACT
BACKGROUND:
The role of the unfolded protein response (UPR) has been progressively unveiled over the last decade and several studies have investigated its implication in glioblastoma (GB) development. The UPR restores cellular homeostasis by triggering the folding and clearance of accumulated misfolded proteins in the ER consecutive to endoplasmic reticulum stress. In case it is overwhelmed, it induces apoptotic cell death. Thus, holding a critical role in cell fate decisions.METHODS:
This article, reviews how the UPR is implicated in cell homeostasis maintenance, then surveils the evidence supporting the UPR involvement in GB genesis, progression, angiogenesis, GB stem cell biology, tumor microenvironment modulation, extracellular matrix remodeling, cell fate decision, invasiveness, and grading. Next, it concurs the evidence showing how the UPR mediates GB chemoresistance-related mechanisms.RESULTS:
The UPR stress sensors IRE1, PERK, and ATF6 with their regulator GRP78 are upregulated in GB compared to lower grade gliomas and normal brain tissue. They are activated in response to oncogenes and are implicated at different stages of GB progression, from its genesis to chemoresistance and relapse. The UPR arms can be effectors of apoptosis as mediators or targets.CONCLUSION:
Recent research has established the role of the UPR in GB pathophysiology and chemoresistance. Targeting its different sensors have shown promising in overcoming GB chomo- and radioresistance and inducing apoptosis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Encefálicas
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Glioblastoma
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Resistencia a Antineoplásicos
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Respuesta de Proteína Desplegada
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Chaperón BiP del Retículo Endoplásmico
Límite:
Animals
/
Humans
Idioma:
En
Revista:
CNS Neurosci Ther
Asunto de la revista:
NEUROLOGIA
/
TERAPEUTICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China