B4GALT1-dependent galectin-8 binding with TGF-ß receptor suppresses colorectal cancer progression and metastasis.
Cell Death Dis
; 15(9): 654, 2024 Sep 04.
Article
en En
| MEDLINE
| ID: mdl-39231945
ABSTRACT
Transforming growth factor (TGF)-ß signaling is critical for epithelial-mesenchymal transition (EMT) and colorectal cancer (CRC) metastasis. Disruption of Smad-depednent TGF-ß signaling has been shown in CRC cells. However, TGF-ß receptor remains expressed on CRC cells. Here, we investigated whether the cooperation between tumor-associated N-glycosylation and a glycan-binding protein modulated the TGF-ß-driven signaling and metastasis of CRC. We showed that galectin-8, a galactose-binding lectin, hampered TGF-ß-induced EMT by interacting with the type II TGF-ß receptor and competing with TGF-ß binding. Depletion of galectin-8 promoted the migration of CRC cells by increasing TGF-ß-receptor-mediated RAS and Src signaling, which was attenuated after recombinant galectin-8 treatment. Treatment with recombinant galectin-8 also induces JNK-dependent apoptosis in CRC cells. The anti-migratory effect of galectin-8 depended on ß4-galactosyltransferase-I (B4GALT1), an enzyme involved in N-glycan synthesis. Increased B4GALT1 expression was observed in clinical CRC samples. Depletion of B4GALT1 reduced the metastatic potential of CRC cells. Furthermore, inducible expression of galectin-8 attenuated tumor development and metastasis of CRC cells in an intra-splenic injection model. Our results thus demonstrate that galectin-8 alters non-canonical TGF-ß response in CRC cells and suppresses CRC progression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Movimiento Celular
/
Galectinas
/
Transición Epitelial-Mesenquimal
/
Galactosiltransferasas
/
Metástasis de la Neoplasia
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Dis
/
Cell death and disease
Año:
2024
Tipo del documento:
Article
País de afiliación:
Taiwán
Pais de publicación:
Reino Unido