Transcription factor 7 like 2 promotes metastasis in hepatocellular carcinoma via NEDD9-mediated activation of AKT/mTOR signaling pathway.
Mol Med
; 30(1): 108, 2024 Jul 25.
Article
en En
| MEDLINE
| ID: mdl-39060928
ABSTRACT
BACKGROUND:
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system, and the exact mechanism of HCC is still unclear. Transcription factor 7 like 2 (TCF7L2) plays a pivotal role in cell proliferation and stemness maintenance. However, the exact mechanism of TCF7L2 in HCC remains unclear.METHODS:
Clinical samples and public databases were used to analyze the expression and prognosis of TCF7L2 in HCC. The function of TCF7L2 in HCC was studied in vitro and in vivo. ChIP and luciferase assays were used to explore the molecular mechanism of TCF7L2. The relationship between TCF7L2 and NEDD9 was verified in HCC clinical samples by tissue microarrays.RESULTS:
The expression of TCF7L2 was upregulated in HCC, and high expression of TCF7L2 was associated with poor prognosis of HCC patients. Overexpression of TCF7L2 promoted the metastasis of HCC in vitro and in vivo, while Knockdown of TCF7L2 showed the opposite effect. Mechanically, TCF7L2 activated neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) transcription by binding to the -1522/-1509 site of the NEDD9 promoter region, thereby increasing the phosphorylation levels of AKT and mTOR. The combination of TCF7L2 and NEDD9 could distinguish the survival of HCC patients.CONCLUSIONS:
This study demonstrated that TCF7L2 promotes HCC metastasis by activating AKT/mTOR pathway in a NEDD9-dependent manner, suggesting that potential of TCF7L2 and NEDD9 as prognostic markers and therapeutic targets for HCC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Regulación Neoplásica de la Expresión Génica
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Carcinoma Hepatocelular
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Proteínas Adaptadoras Transductoras de Señales
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Proteínas Proto-Oncogénicas c-akt
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Serina-Treonina Quinasas TOR
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Proteína 2 Similar al Factor de Transcripción 7
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Neoplasias Hepáticas
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article
País de afiliación:
China