LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects
| Primer Autor |
Gonzalez-Chavarria, Ivan
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| Co-autores |
Duprat, Felix
Robles, Catalina
Castillo, Maria Paz
Rivas, Yerko
Mondaca, Marcela
Jara, Nery
Roa, Francisco
Bertinat, Romina
Toledo, Jorge
Paz, Cristian
|
| Título |
LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects
|
| Editorial |
MDPI
|
| Revista |
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
|
| Lenguaje |
en
|
| Resumen |
The oxidized low-density lipoprotein receptor 1 (LOX-1) is one of the most important receptors for modified LDLs, such as oxidated (oxLDL) and acetylated (acLDL) low-density lipoprotein. LOX-1 and oxLDL are fundamental in atherosclerosis, where oxLDL/LOX1 promotes ROS generation and NF-kappa B activation inducing the expression of IL-6, a STAT3 activator. Furthermore, LOX-1/oxLDL function has been associated with other diseases, such as obesity, hypertension, and cancer. In prostate cancer (CaP), LOX-1 overexpression is associated with advanced stages, and its activation by oxLDL induces an epithelial-mesenchymal transition, increasing angiogenesis and proliferation. Interestingly, enzalutamide-resistant CaP cells increase the uptake of acLDL. Enzalutamide is an androgen receptor (AR) antagonist for castration-resistant prostate cancer (CRPC) treatment, and a high percentage of patients develop a resistance to this drug. The decreased cytotoxicity is promoted in part by STAT3 and NF-kappa B activation that induces the secretion of the pro-inflammatory program and the expression of AR and its splicing variant AR-V7. Here, we demonstrate for the first time that oxLDL/LOX-1 increases ROS levels and activates NF-kappa B, inducing IL-6 secretion and the activation of STAT3 in CRPC cells. Furthermore, oxLDL/LOX1 increases AR and AR-V7 expression and decreases enzalutamide cytotoxicity in CRPC. Thus, our investigation suggests that new factors associated with cardiovascular pathologies, such as LOX-1/oxLDL, may also promote important signaling axes for the progression of CRPC and its resistance to drugs used for its treatment.
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| Fecha Publicación |
2023
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| Tipo de Recurso |
artículo original
|
| doi |
10.3390/ijms24065082
|
| Formato Recurso |
PDF
|
| Palabras Claves |
prostate cancer
castration-resistant prostate cancer
oxLDL
LOX-1
enzalutamide
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| Ubicación del archivo | |
| Categoría OCDE |
Bioquímica y biología molecular
Química
|
| Materias |
Cancer de prostata
cáncer de próstata resistente a la castración
LDLox
LOX-1
enzalutamida
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| Identificador del recurso (Mandatado-único) |
artículo original
|
| Versión del recurso (Recomendado-único) |
versión publicada
|
| License |
CC BY 4.0
|
| Condición de la licencia (Recomendado-repetible) |
CC BY 4.0
|
| Derechos de acceso |
acceso abierto
|
| Access Rights |
acceso abierto
|
| Id de Web of Science |
WOS:000958277600001
|
| Tipo de ruta |
verde# dorado
|
| Categoría WOS |
Bioquímica y biología molecular
Química
|
| Referencia del Financiador (Mandatado si es aplicable-repetible) |
ANID-FONDECYT 11181105
ANID-FONDECYT 11191195
ANID-FONDECYT 1201217
ANID FONDECYT 11181105
ANID FONDECYT 11191195
ANID FONDECYT 1201217
|
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