GLI2 but not GLI1/GLI3 plays a central role in the induction of malignant phenotype of gallbladder cancer.
Oncol Rep
; 45(3): 997-1010, 2021 03.
Article
en En
| MEDLINE
| ID: mdl-33650666
ABSTRACT
We previously reported that Hedgehog (Hh) signal was enhanced in gallbladder cancer (GBC) and was involved in the induction of malignant phenotype of GBC. In recent years, therapeutics that target Hh signaling have focused on molecules downstream of smoothened (SMO). The three transcription factors in the Hh signal pathway, gliomaassociated oncogene homolog 1 (GLI1), GLI2, and GLI3, function downstream of SMO, but their biological role in GBC remains unclear. In the present study, the biological significance of GLI1, GLI2, and GLI3 were analyzed with the aim of developing novel treatments for GBC. It was revealed that GLI2, but not GLI1 or GLI3, was involved in the cell cyclemediated proliferative capacity in GBC and that GLI2, but not GLI1 or GLI3, was involved in the enhanced invasive capacity through epithelialmesenchymal transition. Further analyses revealed that GLI2 may function in mediating gemcitabine sensitivity and that GLI2 was involved in the promotion of fibrosis in a mouse xenograft model. Immunohistochemical staining of 66 surgically resected GBC tissues revealed that GLI2high expression patients had fewer numbers of CD3+ and CD8+ tumorinfiltrating lymphocytes (TILs) and increased programmed cell death ligand 1 (PDL1) expression in cancer cells. These results suggest that GLI2, but not GLI1 or GLI3, is involved in proliferation, invasion, fibrosis, PDL1 expression, and TILs in GBC and could be a novel therapeutic target. The results of this study provide a significant contribution to the development of a new treatment for refractory GBC, which has few therapeutic options.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
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Proteína Gli2 con Dedos de Zinc
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Neoplasias de la Vesícula Biliar
Tipo de estudio:
Prognostic_studies
Límite:
Aged
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Animals
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón