Volume-regulated anion channel as a novel cancer therapeutic target

Int J Biol Macromol. 2020 Sep 15:159:570-576. doi: 10.1016/j.ijbiomac.2020.05.137. Epub 2020 May 20.

Abstract

Volume-regulated anion channel (VRAC) is ubiquitously expressed in vertebrate cells and in various types of cancer cells. Leucine-rich repeat containing 8A (LRRC8A) and its four homologous family members (LRRC8B-E) assemble into heterogeneous VRAC complexes of ~800 kDa. The main components of VRAC, LRRC8A and LRRC8D have been implicated in the proliferation, migration, death, and multidrug resistance of cancer cells through their involvement in various signal pathways. This review summarizes recent findings concerning the involvement of VRAC in cancer development and progression, including the molecular structure, function, and regulation of VRAC and its roles in various cancers, and highlights the remaining challenges in the field. Our aim is to evaluate the potential of VRAC as a therapeutic target for cancer therapies and to discuss the major problems to be solved.

Keywords: Cell proliferation; LRRC8; Migration; Multidrug resistance; VRAC.

Publication types

  • Review

MeSH terms

  • Animals
  • Anion Transport Proteins / antagonists & inhibitors
  • Anion Transport Proteins / chemistry
  • Anion Transport Proteins / genetics
  • Anion Transport Proteins / metabolism*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor*
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Protein Binding
  • Protein Multimerization
  • Signal Transduction / drug effects

Substances

  • Anion Transport Proteins
  • Antineoplastic Agents
  • Biomarkers, Tumor