In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer

Academic Article

Abstract

  • Genetic aberrations driving pro-oncogenic and pro-metastatic activity remain an elusive target in the quest of precision oncology. To identify such drivers, we use an animal model of KRAS-mutant lung adenocarcinoma to perform an in vivo functional screen of 217 genetic aberrations selected from lung cancer genomics datasets. We identify 28 genes whose expression promoted tumor metastasis to the lung in mice. We employ two tools for examining the KRAS-dependence of genes identified from our screen: 1) a human lung cell model containing a regulatable mutant KRAS allele and 2) a lentiviral system permitting co-expression of DNA-barcoded cDNAs with Cre recombinase to activate a mutant KRAS allele in the lungs of mice. Mechanistic evaluation of one gene, GATAD2B, illuminates its role as a dual activity gene, promoting both pro-tumorigenic and pro-metastatic activities in KRAS-mutant lung cancer through interaction with c-MYC and hyperactivation of the c-MYC pathway.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Grzeskowiak CL; Kundu ST; Mo X; Ivanov AA; Zagorodna O; Lu H; Chapple RH; Tsang YH; Moreno D; Mosqueda M
  • Volume

  • 9
  • Issue

  • 1