GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma / 医学前沿
Frontiers of Medicine
; (4): 119-131, 2023.
Article
em En
| WPRIM
| ID: wpr-971625
Biblioteca responsável:
WPRO
ABSTRACT
Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.
Palavras-chave
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Neoplasias Esofágicas
/
Carcinoma de Células Escamosas
/
Regulação Neoplásica da Expressão Gênica
/
Cisplatino
/
Linhagem Celular Tumoral
/
Proliferação de Células
/
Proteínas Proto-Oncogênicas c-akt
/
Fator 15 de Diferenciação de Crescimento
/
Carcinoma de Células Escamosas do Esôfago
/
Receptor do Fator de Crescimento Transformador beta Tipo II
Limite:
Humans
Idioma:
En
Revista:
Frontiers of Medicine
Ano de publicação:
2023
Tipo de documento:
Article