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International journal of molecular sciences
Jan 14, 2021;22 (2):

Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy.

Qi Liu, Bayonle Aminu, Olivia Roscow, Wei Zhang
Author Information
  1. Qi Liu: Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, 50 Stone Rd E, Guelph, ON N1G2W1, Canada.
  2. Bayonle Aminu: Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, 50 Stone Rd E, Guelph, ON N1G2W1, Canada.
  3. Olivia Roscow: Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, 50 Stone Rd E, Guelph, ON N1G2W1, Canada.
  4. Wei Zhang: Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, 50 Stone Rd E, Guelph, ON N1G2W1, Canada.
PMID: 33466790 DOI: 10.3390/ijms22020791

Abstract

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.

Keywords

E3 ligase cancer-associated fibroblasts deubiquitinase extracellular matrix hypoxia immune cells inhibitors tumor microenvironment ubiquitin variants ubiquitination

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Grants

  1. 23665/Cancer Research Society

MeSH Term

Angiogenesis Inhibitors
Humans
Neoplasms
Signal Transduction
Small Molecule Libraries
Tumor Microenvironment
Ubiquitin
Ubiquitin-Activating Enzymes
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligases
Ubiquitination

Chemicals

Angiogenesis Inhibitors
Small Molecule Libraries
Ubiquitin
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligases
Ubiquitin-Activating Enzymes
Journal Article Review

Word Cloud

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