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      NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy

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          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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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Autophagy: renovation of cells and tissues.

            Noboru Mizushima, Masaaki Komatsu (2011)
            Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Global epidemiology of oral and oropharyngeal cancer.

              Saman Warnakulasuriya (2008)
              This review presents data on incidence, mortality, survival and trends in cancers of the lip, oral cavity and oropharynx using available recent data sources around the world. Oral and pharyngeal cancer, grouped together, is the sixth most common cancer in the world. The review focuses primarily on several high-risk countries in an attempt to gain insight into the geographic variations in the incidence of this cancer in the globe and to relate the high incidence in some populations to their life style. With an estimated half a million cases around the globe and the rising trends reported in some populations, particularly in the young, urgent public health measures are needed to reduce the incidence and mortality of oral and oropharyngeal cancer.
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                Author and article information

                Contributors
                Huifeng Pi: pihuifeng2010@163.com
                Zhou Zhou: lunazhou@zju.edu.cn
                Zhiyuan Zhang: zhzhy0502@163.com
                Journal
                Journal ID (nlm-ta): Signal Transduct Target Ther
                Journal ID (iso-abbrev): Signal Transduct Target Ther
                Title: Signal Transduction and Targeted Therapy
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 2095-9907
                ISSN (Electronic): 2059-3635
                Publication date (Electronic): 25 April 2022
                Publication date PMC-release: 25 April 2022
                Publication date Collection: 2022
                Volume: 7
                Electronic Location Identifier: 130
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Oral and Maxillofacial-Head Neck Oncology, , Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, ; Shanghai, China
                [2 ]GRID grid.412523.3, Department of Oral and Maxillofacial Surgery, , Zhang Zhiyuan Academician Workstation, Hainan Western Central Hospital, Shanghai Ninth People’s Hospital, ; Danzhou, Hainan China
                [3 ]GRID grid.452708.c, ISNI 0000 0004 1803 0208, Department of Oral and Maxillofacial Surgery, , The Second Xiangya Hospital of Central South University, ; Changsha, Hunan China
                [4 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Oral Pathology, , Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, ; Shanghai, China
                [5 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Occupational Health, , Third Military Medical University, ; Chongqing, China
                [6 ]GRID grid.452708.c, ISNI 0000 0004 1803 0208, Department of Pathology, , The Second Xiangya Hospital of Central South University, ; Changsha, Hunan China
                [7 ]GRID grid.256609.e, ISNI 0000 0001 2254 5798, School of Medicine, , Guangxi University, ; Nanning, Guangxi Zhuang Autonomous Region China
                [8 ]GRID grid.443385.d, ISNI 0000 0004 1798 9548, Department of Oral and Maxillofacial Surgery, , Affiliated Hospital of Guilin Medical University, ; Guilin, Guangxi Zhuang Autonomous Region China
                [9 ]GRID grid.416208.9, ISNI 0000 0004 1757 2259, Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, ; Chongqing, China
                [10 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Department of Emergency Medicine, , First Affiliated Hospital and Department of Environmental Medicine, School of Public Health, School of Medicine, Zhejiang University, ; Hangzhou, Zhejiang China
                Article
                Publisher ID: 939
                DOI: 10.1038/s41392-022-00939-7
                PMC ID: 9035452
                PubMed ID: 35462576
                SO-VID: 647d6750-a557-4adc-889b-63054abf23e4
                Copyright © © The Author(s) 2022
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 10 November 2021
                Date revision received : 11 February 2022
                Date accepted : 22 February 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81802716
                Award ID: 32000552
                Award Recipient :
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2022

                Keywords: head and neck cancer
                Data availability:
                Keywords: head and neck cancer

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