Deletion of Glutathione S-Transferase Omega 1 Activates Type I Interferon Genes and Downregulates Tissue Factor.

ABSTRACT: GST omega 1 (GSTO1) is an atypical GST isoform that is overexpressed in several cancers and has been implicated in drug resistance. Currently, no small-molecule drug targeting GSTO1 is under clinical development. Here we have validated GSTO1 as an impactful target in oncology. Transcriptional profiling coupled with proteomics uncovered novel pharmacodynamic markers and cellular pathways regulated by GSTO1. CRISPR/Cas9 GSTO1 knockout (KO) cell lines failed to form tumors or displayed growth delay in vivo; they also formed smaller 3D spheroids in vitro. Multiomics analysis in GSTO1 KO cells found a strong positive correlation with cell adhesion molecules and IFN response pathways and a strong negative correlation with Myc transcriptional signature. In addition, several clinical

SUBMITTER: Xu Y 

PROVIDER: S-EPMC7483942 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature