PDK1 promotes metastasis by inducing epithelial-mesenchymal transition in hypopharyngeal carcinoma via the Notch1 signaling pathway.
Exp Cell Res
; 386(2): 111746, 2020 01 15.
Article
en En
| MEDLINE
| ID: mdl-31778670
ABSTRACT
Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare malignancy and has the worst prognosis among head and neck cancer. Metastasis is the major cause of poor prognosis in HSCC patients. In this study, we found that 3-phosphoinositide-dependent protein kinase 1 (PDK1 or PDPK1) was overexpressed in HSCC. The overexpression was positively correlated lymph node metastasis, clinical stage, and distant metastasis and indicated poor outcome. Loss and gain-of-function revealed that PDK1 increased cell proliferation, migration and invasion in vitro as well as tumor growth and metastasis in vivo. Mechanically, PDK1 induced epithelial-mesenchymal transition and promoted metastasis by activating the Notch1 signaling pathway. We further illustrated that PDK1 bound with the Notch1 intracellular domain, thereby inhibiting its ubiquitin-mediated degradation in a protein kinase B (Akt-) independent manner. In summary, PDK1/Notch1 axis played an important role in HSCC metastasis, and this investigation provided a new perspective on potential therapeutic targets for HSCC.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Escamosas
/
Neoplasias Hipofaríngeas
/
Regulación Neoplásica de la Expresión Génica
/
Receptor Notch1
/
Transición Epitelial-Mesenquimal
/
Proteínas Quinasas Dependientes de 3-Fosfoinosítido
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Exp Cell Res
Año:
2020
Tipo del documento:
Article