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Role of SUMO activating enzyme in cancer stem cell maintenance and self-renewal

Author

Listed:
  • Li Du

    (Beckman Research Institute of City of Hope)

  • Yi-Jia Li

    (Beckman Research Institute of City of Hope)

  • Marwan Fakih

    (City of Hope National Medical Center)

  • Rebecca L. Wiatrek

    (City of Hope National Medical Center
    Present address: Texas Oncology, Austin, Texas, USA)

  • Marjun Duldulao

    (City of Hope National Medical Center
    Present address: Memorial Sloan Kettering Cancer Center, New York, New York, USA)

  • Zhenbin Chen

    (City of Hope National Medical Center
    Present address: University of Alabama at Birmingham, Birmingham, Alabama, USA)

  • Peiguo Chu

    (City of Hope National Medical Center)

  • Julio Garcia-Aguilar

    (City of Hope National Medical Center
    Present address: Memorial Sloan Kettering Cancer Center, New York, New York, USA)

  • Yuan Chen

    (Beckman Research Institute of City of Hope)

Abstract

Cancer stem cells (CSCs) have key roles in treatment resistance, tumour metastasis and relapse. Using colorectal cancer (CC) cell lines, patient-derived xenograft (PDX) tissues and patient tissues, here we report that CC CSCs, which resist chemoradiation, have higher SUMO activating enzyme (E1) and global SUMOylation levels than non-CSCs. Knockdown of SUMO E1 or SUMO conjugating enzyme (E2) inhibits CC CSC maintenance and self-renewal, while overexpression of SUMO E1 or E2 increases CC cell stemness. We found that SUMOylation regulates CSCs through Oct-1, a transcription factor for aldehyde dehydrogenases (ALDHs). ALDH activity is not only a marker for CSCs but also important in CSC biology. SUMO does not modify Oct-1 directly, but regulates the expression of TRIM21 that enhances Oct-1 ubiquitination and, consequently, reducing Oct-1 stability. In summary, our findings suggest that SUMOylation could be a target to inhibit CSCs and ultimately to reduce treatment resistance, tumour metastasis and relapse.

Suggested Citation

  • Li Du & Yi-Jia Li & Marwan Fakih & Rebecca L. Wiatrek & Marjun Duldulao & Zhenbin Chen & Peiguo Chu & Julio Garcia-Aguilar & Yuan Chen, 2016. "Role of SUMO activating enzyme in cancer stem cell maintenance and self-renewal," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12326
    DOI: 10.1038/ncomms12326
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    Cited by:

    1. Qiuhong Zhu & Panpan Liang & Hao Meng & Fangzhen Li & Wei Miao & Cuiying Chu & Wei Wang & Dongxue Li & Cong Chen & Yu Shi & Xingjiang Yu & Yifang Ping & Chaoshi Niu & Hai-bo Wu & Aili Zhang & Xiu-wu B, 2024. "Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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