Galectin-3 Interacts with C/EBPß and Upregulates Hyaluronan-Mediated Motility Receptor Expression in Gastric Cancer.
Mol Cancer Res
; 18(3): 403-413, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31822520
ABSTRACT
The hyaluronan-mediated motility receptor (HMMR) is overexpressed in gastric cancer; however, the apparent role of HMMR has not been well defined owing to lack of detailed studies on gastric tumorigenesis. Therefore, we elucidated the functional and regulatory mechanisms of HMMR in gastric cancer. Using publicly available data, we confirmed HMMR overexpression in patients with gastric cancer. HMMR silencing decreased proliferation, migration, and invasion of gastric cancer cells, whereas HMMR overexpression reversed these effects. A gastric cancer xenograft mouse model showed statistically significant inhibition of tumor growth upon HMMR depletion. Previous data from cDNA microarray showed reduced HMMR expression upon inhibition of galectin-3. However, overexpression of galectin-3 increased HMMR expression, cell proliferation, and motility in gastric cancer cells, whereas HMMR silencing blocked these effects. Interestingly, galectin-3 interacted directly with C/EBPß and bound to HMMR promoter to drive its transcription, and gastric cancer cell proliferation and motility. Altogether, high expression of HMMR promoted gastric cancer cell proliferation and motility and could be a prognostic factor in gastric cancer. In addition, HMMR expression was regulated by the interaction between C/EBPß and galectin-3. Therefore, targeting HMMR along with galectin-3 and C/EBPß complex could be a potential treatment strategy for inhibiting gastric cancer progression and metastasis. IMPLICATIONS This study provides evidence that galectin-3 interacts with C/EBPß in gastric cancer, and galectin-3 and C/EBPß complex promotes gastric cancer cell progression and motility through upregulating HMMR expression.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Proteína beta Potenciadora de Unión a CCAAT
/
Galectina 3
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cancer Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article