E3 ubiquitin ligases and deubiquitinases in colorectal cancer: Emerging molecular insights and therapeutic opportunities

Biochim Biophys Acta Mol Cell Res. 2024 Dec;1871(8):119827. doi: 10.1016/j.bbamcr.2024.119827. Epub 2024 Aug 24.

Abstract

Colorectal cancer (CRC) presents ongoing challenges due to limited treatment effectiveness and a discouraging prognosis, underscoring the need for ground-breaking therapeutic approaches. This review delves into the pivotal role of E3 ubiquitin ligases and deubiquitinases (DUBs), underscoring their role as crucial regulators for tumor suppression and oncogenesis in CRC. We spotlight the diverse impact of E3 ligases and DUBs on CRC's biological processes and their remarkable versatility. We closely examine their specific influence on vital signaling pathways, particularly Wnt/β-catenin and NF-κB. Understanding these regulatory mechanisms is crucial for unravelling the complexities of CRC progression. Importantly, we explore the untapped potential of E3 ligases and DUBs as novel CRC treatment targets, discussing aspects that may guide more effective therapeutic strategies. In conclusion, our concise review illuminates the E3 ubiquitin ligases and deubiquitinases pivotal role in CRC, offering insights to inspire innovative approaches for transforming the treatment landscape in CRC.

Keywords: Cancer hallmarks; Colorectal cancer (CRC); DUBTACs; Deubiquitinases; E3 ubiquitin ligases; PROTACs; Signaling pathways.

Publication types

  • Review

MeSH terms

  • Animals
  • Colorectal Neoplasms* / enzymology
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms* / therapy
  • Deubiquitinating Enzymes* / metabolism
  • Humans
  • NF-kappa B / metabolism
  • Signal Transduction
  • Ubiquitin-Protein Ligases* / genetics
  • Ubiquitin-Protein Ligases* / metabolism
  • Ubiquitination
  • Wnt Signaling Pathway

Substances

  • Ubiquitin-Protein Ligases
  • Deubiquitinating Enzymes
  • NF-kappa B