GCN2: roles in tumour development and progression

Lyssa T. Gold, Glenn Masson (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)
46 Downloads (Pure)

Abstract

GCN2 (general control nonderepessible 2) is an eIF2α kinase responsible for entirely rewiring the metabolism of cells when they are put under amino acid starvation stress. Recently, there has been renewed interest in GCN2 as a potential oncotarget, with several studies reporting the development of small molecule inhibitors. The foundation of this work is built upon biochemical and cellular data which suggest GCN2 may be aberrantly overexpressed and is responsible for keeping cells on ‘life-support’ while tumours undergo significant nutritional stress during tumorigenesis, allowing cancer stem cells to develop chemotherapeutic resistance. However, most studies which have investigated the role of GCN2 in cancer have been conducted in various cancer model systems, often under a specific set of stresses, mutational backgrounds and drug cocktails. This review aims to comprehensively summarise the biochemical, molecular and cellular literature associated with GCN2 and its role in various cancers and determine whether a consensus can be developed to discern under which circumstances we may wish to target
GCN2.
Original languageEnglish
Pages (from-to)737-745
Number of pages9
JournalBiochemical Society Transactions
Volume50
Issue number2
Early online date21 Mar 2022
DOIs
Publication statusPublished - 21 Mar 2022

Keywords

  • cancer signalling
  • GCN2
  • integrate stress response
  • starvation signaling

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