@article{3d942de48ea74cd4a71df1b88ee22bfb,
title = "In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer",
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.",
author = "Grzeskowiak, {Caitlin L.} and Kundu, {Samrat T.} and Xiulei Mo and Ivanov, {Andrei A.} and Oksana Zagorodna and Hengyu Lu and Chapple, {Richard H.} and Tsang, {Yiu Huen} and Daniela Moreno and Maribel Mosqueda and Karina Eterovic and Fradette, {Jared J.} and Sumreen Ahmad and Fengju Chen and Zechen Chong and Ken Chen and Creighton, {Chad J.} and Haian Fu and Mills, {Gordon B.} and Gibbons, {Don L.} and Scott, {Kenneth L.}",
note = "Funding Information: The authors would like to thank Dr. John Minna (UT Southwestern) for providing parental Human Bronchial Epithelial Cell lines. C.G. also wishes to thank Dr. Sharon Plon for her guidance and mentorship during this project and in review of this manuscript This project was supported in part by the Genomic and RNA Profiling Core at Baylor College of Medicine with funding from the NIH/NCI grant (P30CA125123) and Cytometry and Cell Sorting Core Facility with funding from the NIH (P30 AI036211, P30 CA125123, and S10 RR024574). This project was also supported by the Cancer Prevention and Research Institute of Texas (CPRIT; RP140216) by funding to K.L.S., the Department of Defense (LC110216) by funding to K..L.S. and D.LG., an MD Anderson Cancer Center Physician Scientist Award to D.L.G., and by the NIH (U01CA168394) by funding to K..L.S. and G.B.M. H. L. was supported by the CPRIT Pre-Doctoral Fellowship (RP140102). D.L.G. is a Lee Clark Fellow of the University of Texas MD Anderson Cancer Center. This project was also supported by the Cancer Target Discovery and Development Network grants U01CA168449 and U01CA217875 to H.F. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-04572-3",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}