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Transcription factor 7 like 2 promotes metastasis in hepatocellular carcinoma via NEDD9-mediated activation of AKT/mTOR signaling pathway.
Tang, Linsong; Xu, Shengjun; Wei, Rongli; Fan, Guanghan; Zhou, Junbin; Wei, Xuyong; Xu, Xiao.
Afiliación
  • Tang L; Department of Urology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • Xu S; NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, Zhejiang, China.
  • Wei R; Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • Fan G; Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
  • Zhou J; NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, Zhejiang, China.
  • Wei X; Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
  • Xu X; Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Carcinoma Hepatocelular / Proteínas Adaptadoras Transductoras de Señales / Proteínas Proto-Oncogénicas c-akt / Serina-Treonina Quinasas TOR / Proteína 2 Similar al Factor de Transcripción 7 / Neoplasias Hepáticas Límite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Carcinoma Hepatocelular / Proteínas Adaptadoras Transductoras de Señales / Proteínas Proto-Oncogénicas c-akt / Serina-Treonina Quinasas TOR / Proteína 2 Similar al Factor de Transcripción 7 / Neoplasias Hepáticas Límite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido