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Tumor Promoting Function of DUSP10 in Non-Small Cell Lung Cancer Is Associated With Tumor-Promoting Cytokines

  • Xing Wei (Breast Surgery Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)) ;
  • Chin Wen Png (Department of Microbiology and Immunology, and NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Madhushanee Weerasooriya (Department of Microbiology and Immunology, and NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Heng Li (Department of Microbiology and Immunology, and NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Chenchen Zhu (Breast Surgery Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)) ;
  • Guiping Chen (Breast Surgery Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)) ;
  • Chuan Xu (Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Yongliang Zhang (Department of Microbiology and Immunology, and NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Xiaohong Xu (Breast Surgery Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine))
  • Received : 2023.04.30
  • Accepted : 2023.07.31
  • Published : 2023.08.31
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Abstract

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

Keywords

Acknowledgement

This work was supported by grants from the TCM Science and Technology Program of Zhejiang Province, China (2020ZA054/2020 to G.C.), and the Science and Technology Project of Zunyi, Guizhou province, China (Zunyi City Kehe Support NS (2020) No. 18/2020 to X.X.), the Singapore National Medical Research Council (NMRC/OFIRG/0059/2017 to Y. Z.) and the National University Health System (NUHSRO/2021/110/T1/Seed-Sep/03 to C.W. P.).

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