Isoforms of the orphan nuclear receptor COUPTFII differentially modulate pancreatic cancer progression.
Int J Oncol
; 60(5)2022 May.
Article
em En
| MEDLINE
| ID: mdl-35348189
ABSTRACT
The expression of the nuclear receptor transcription factor (TF) COUPTFII is broadly associated with cell differentiation and cancer development, including of pancreatic ductal adenocarcinoma (PDAC), a devastating disease with one of the poorest prognoses among cancers worldwide. Recent studies have started to investigate the pathological and physiological roles of a novel COUPTFII isoform (COUPTFII_V2) that lacks the DNAbinding domain. As the role of the canonical COUPTFII in PDAC was previously demonstrated, the present study evaluated whether COUPTFII_V2 may have a functional role in PDAC. It was demonstrated that COUPTFII_V2 naturally occurs in PDAC cells and in primary samples, where its expression is consistent with shorter overall survival and peripheral invasion. Of note, COUPTFII_V2, exhibiting nuclear and cytosolic expression, is linked to epithelial to mesenchymal transition (EMT) and cancer progression, as confirmed by nude mouse experiments. The present results demonstrated that COUPTFII_V2 distinctively regulates the EMT of PDAC and, similarly to its sibling, it is associated with tumor aggressiveness. The two isoforms have both overlapping and exclusive functions that cooperate with cancer growth and dissemination. By studying how PDAC cells switch from one isoform to the other, novel insight into cancer biology was gained, indicating that this receptor may serve as a novel possible target for PDAC management.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Carcinoma Ductal Pancreático
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Fator II de Transcrição COUP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article