NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy.
NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy.
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DOI：
10.1038/s41392-022-00939-7
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发表时间：
2022-04-25
影响因子：
39.3
通讯作者：
Zhang, Zhiyuan
中科院分区：
文献类型：
--
作者：
Fan, Tengfei;Wang, Xiaoning;Zhang, Sheng;Deng, Ping;Jiang, Yi;Liang, Yidan;Jie, Sheng;Wang, Qing;Li, Chuwen;Tian, Guocai;Zhang, Zhen;Ren, Zhenhu;Li, Bo;Chen, Yanrong;He, Zhijing;Luo, Yan;Chen, Mingliang;Wu, Hanjiang;Yu, Zhengping;Pi, Huifeng;Zhou, Zhou;Zhang, Zhiyuan
口腔鳞状细胞癌(OSCC)是最常见的口腔恶性肿瘤，转移是OSCC预后较差的原因之一。自噬被认为通过减轻各种细胞压力来促进口腔鳞状细胞癌的发展；然而，自噬在口腔鳞癌细胞增殖和转移中的机制尚不清楚。在我们的研究中，高灵敏度的无标记定量蛋白质组学分析显示，核蛋白1(NUPR1)是福尔马林固定的石蜡包埋肿瘤样本中最显著上调的蛋白质，来自有或没有淋巴转移的口腔鳞癌患者。此外，NUPR1在口腔鳞癌组织中异常表达，预示着口腔鳞癌患者的总体生存率较低。值得注意的是，基于串联质量标签的定量蛋白质组学分析，我们证实了NUPR1通过直接提高转录因子E3(TFE3)的活性来维持自噬通量和溶酶体功能，从而促进了口腔鳞癌细胞的体外和体内的增殖和转移。总之，我们的数据显示，NUPR1-TFE3轴是口腔鳞癌进展过程中自噬机制的关键调节因子，本研究可能为口腔鳞癌的治疗提供一个潜在的治疗靶点。
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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影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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