NUPR1 Promotes the Proliferation and Metastasis of Oral Squamous Cell Carcinoma Cells by Activating TFE3-dependent Autophagy

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2022 Apr 25

PMID 35462576

Authors

Tengfei Fan

Xiaoning Wang

Sheng Zhang

Ping Deng

Yi Jiang

Yidan Liang

Sheng Jie

Qing Wang

Chuwen Li

Guocai Tian

Zhen Zhang

Zhenhu Ren

Bo Li

Yanrong Chen

Zhijing He

Yan Luo

Mingliang Chen

Hanjiang Wu

Zhengping Yu

Huifeng Pi

Zhou Zhou

Zhiyuan Zhang

Affiliations

Soon will be listed here.

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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