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Experimental hematology & oncology
Mar 30, 2023;12 (1): 34.

Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy.

Xian-Miao Li, Zhen-Yu Zhao, Xiao Yu, Qi-Dong Xia, Peng Zhou, Shao-Gang Wang, Huan-Lei Wu, Jia Hu
Author Information
  1. Xian-Miao Li: Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China.
  2. Zhen-Yu Zhao: Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China.
  3. Xiao Yu: Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China.
  4. Qi-Dong Xia: Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China.
  5. Peng Zhou: Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China.
  6. Shao-Gang Wang: Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China.
  7. Huan-Lei Wu: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. wuhuanlei926@163.com.
  8. Jia Hu: Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China. jiahu@tjh.tjmu.edu.cn.
PMID: 36998063 DOI: 10.1186/s40164-023-00394-2

Abstract

Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, and acquire mesenchymal properties that mediate invasion and metastasis. Stromal cells and soluble mediators in the tumor microenvironment (TME) exhibit characteristic anti-inflammatory and protumorigenic activities. Ubiquitination, which is an essential and reversible posttranscriptional modification, plays a vital role in modulating the stability, activity and localization of modified proteins through an enzymatic cascade. This review was motivated by accumulating evidence that a series of E3 ligases and deubiquitinases (DUBs) finely target multiple signaling pathways, transcription factors and key enzymes to govern the functions of almost all components of the TME. In this review, we systematically summarize the key substrate proteins involved in the formation of the TME and the E3 ligases and DUBs that recognize these proteins. In addition, several promising techniques for targeted protein degradation by hijacking the intracellular E3 ubiquitin-ligase machinery are introduced.

Keywords

Cancer therapy Deubiquitinases SUMOylation Tumor microenvironment Ubiquitination

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Grants

  1. 82103177/National Natural Science Foundation of China
  2. 82172586/National Natural Science Foundation of China
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