NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy.
Signal Transduct Target Ther
; 7(1): 130, 2022 04 25.
Article
em En
| MEDLINE
| ID: mdl-35462576
ABSTRACT
Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy, and metastasis accounts for the poor prognosis of OSCC. Autophagy is considered to facilitate OSCC development by mitigating various cellular stresses; nevertheless, the mechanisms of autophagy in OSCC cell proliferation and metastasis remain unknown. In our study, high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1 (NUPR1) as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis. Moreover, NUPR1 is aberrantly expressed in the OSCC tissues and predicts low overall survival rates for OSCC patients. Notably, based on tandem mass tag-based quantitative proteomic analysis between stable NUPR1 knockdown OSCC cells and scrambled control OSCC cells, we confirmed that NUPR1 maintained autophagic flux and lysosomal functions by directly increasing transcription factor E3 (TFE3) activity, which promoted OSCC cell proliferation and metastasis in vitro and in vivo. Collectively, our data revealed that the NUPR1-TFE3 axis is a critical regulator of the autophagic machinery in OSCC progression, and this study may provide a potential therapeutic target for the treatment of OSCC.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Carcinoma de Células Escamosas de Cabeça e Pescoço
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Neoplasias de Cabeça e Pescoço
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Proteínas de Neoplasias
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article