L-GILZ binds and inhibits nuclear factor κB nuclear translocation in undifferentiated thyroid cancer cells.
J Chemother
; 32(5): 263-267, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-32067575
ABSTRACT
Proto-oncogene mutations and abnormal activation of mitogen-activated protein kinase (MAPK) signalling are recurrently found in thyroid cancers. Some thyroid neoplasms respond to drugs that inhibit MAPK pathway activation. Previously, we showed that pharmacological inhibition of MAPK in thyroid cancer cells inhibits cell proliferation and upregulates L-GILZ (long glucocorticoid-induced leucine zipper), a protein with anti-oncogenic and antiproliferative activity, and that L-GILZ is partially responsible for the antiproliferative activity of MAPK inhibitors. Here, we demonstrate that pharmacological inhibition of MAPK in the anaplastic thyroid cancer cell line CAL-62 upregulated L-GILZ, which bound nuclear factor κB (NF-κB) and inhibited its nuclear translocation. These data demonstrate a unique L-GILZ-mediated molecular mechanism that, by trapping NF-κB in the cytoplasm, contributes to the inhibition of proliferation induced by drugs targeting the MAPK transduction cascade. Enhanced knowledge of the mechanism of action of MAPK pathway-inhibiting drugs may improve their clinical use.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Butadienos
/
Neoplasias de la Tiroides
/
FN-kappa B
/
Dominios y Motivos de Interacción de Proteínas
/
Carcinoma Anaplásico de Tiroides
/
Nitrilos
Límite:
Humans
Idioma:
En
Revista:
J Chemother
Asunto de la revista:
ANTINEOPLASICOS
/
TERAPIA POR MEDICAMENTOS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM