Acid/bile exposure triggers TRAIL-mediated apoptosis in esophageal cancer cells by suppressing the decoy receptors and c-FLIPR.
Int J Biochem Cell Biol
; 122: 105736, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32135301
ABSTRACT
Esophageal adenocarcinoma essentially develops from esophageal inflammation caused by chronic GERD. During GERD episodes, the lower esophageal epithelium is repeatedly exposed to stomach acid, which often contains duodenal bile salts that prompt malignant transformation. TRAIL is one of the cytokines produced in response to such insults and targets the transformed cells exclusively. In this study, we simulated GERD episodes in vitro by exposing the cancer cells to acid or acid/bile combination and found that the cancer cells lived through acid attacks by expression of the decoy receptors and c-FLIPR but died of TRAIL-mediated apoptosis when bile salts were present. Further investigation revealed that acid/bile exposure downregulated the decoy receptors and thereby facilitated TRAIL signaling; meantime, it inhibited protein kinase C activity and thus expedited c-FLIPR degradation, allowing apoptosis to take place.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácidos e Sais Biliares
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Neoplasias Esofágicas
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Adenocarcinoma
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Ligante Indutor de Apoptose Relacionado a TNF
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Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
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Receptores Chamariz do Fator de Necrose Tumoral
Limite:
Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China