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DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death

Author

Listed:
  • Heng Boon Low

    (National University of Singapore
    National University of Singapore)

  • Zhen Lim Wong

    (National University of Singapore
    National University of Singapore)

  • Bangyuan Wu

    (National University of Singapore
    National University of Singapore
    China West Normal University)

  • Li Ren Kong

    (National University of Singapore)

  • Chin Wen Png

    (National University of Singapore
    National University of Singapore)

  • Yik-Lam Cho

    (National University of Singapore)

  • Chun-Wei Li

    (The First Affiliated Hospital of Sun Yat-Sen University)

  • Fengchun Xiao

    (The First Affiliated Hospital of Zhejiang Chinese Medical University)

  • Xuan Xin

    (National University of Singapore)

  • Henry Yang

    (National University of Singapore)

  • Jia Min Loo

    (Genome Institute of Singapore, Agency of Science Technology and Research (A*Star))

  • Fiona Yi Xin Lee

    (National Cancer Center)

  • Iain Bee Huat Tan

    (National Cancer Center)

  • Ramanuj DasGupta

    (Genome Institute of Singapore, Agency of Science Technology and Research (A*Star))

  • Han-Ming Shen

    (National University of Singapore
    University of Macau)

  • Herbert Schwarz

    (National University of Singapore
    National University of Singapore)

  • Nicholas R. J. Gascoigne

    (National University of Singapore
    National University of Singapore)

  • Boon Cher Goh

    (National University of Singapore
    National University Cancer Institute
    National University of Singapore)

  • Xiaohong Xu

    (The First Affiliated Hospital of Zhejiang Chinese Medical University)

  • Yongliang Zhang

    (National University of Singapore
    National University of Singapore)

Abstract

Drug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates resistance to chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant to chemotherapy-induced cell death than cells with lower DUSP16 expression. Overexpression of DUSP16 in cancer cells leads to increased resistance to cell death upon chemotherapy treatment. In contrast, knockdown of DUSP16 in cancer cells increases their sensitivity to treatment. Mechanistically, DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria to reduce apoptosis. Analysis of patient survival in head & neck cancer and breast cancer patient cohorts supports DUSP16 as a marker for sensitivity to chemotherapy and therapeutic outcome. This study therefore identifies DUSP16 as a prognostic marker for the efficacy of chemotherapy, and as a therapeutic target for overcoming chemoresistance in cancer.

Suggested Citation

  • Heng Boon Low & Zhen Lim Wong & Bangyuan Wu & Li Ren Kong & Chin Wen Png & Yik-Lam Cho & Chun-Wei Li & Fengchun Xiao & Xuan Xin & Henry Yang & Jia Min Loo & Fiona Yi Xin Lee & Iain Bee Huat Tan & Rama, 2021. "DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22638-7
    DOI: 10.1038/s41467-021-22638-7
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