About this item:

183 Views | 255 Downloads

Author Notes:

Correspondence and requests for materials should be addressed to D.L.G. (email: dlgibbon@mdanderson.org)

Conception and design: C.G., S.T.K., D.L.G. and K.L.S.

Acquisition of data: C.G., S.T.K., O.Z., X.L.M., A.A.I., H.L., R.H.C., Y.H.T., D.M., M.M., K.E., J.J.F., S.A., F.C., Z.C.

Analysis and interpretation of data: C.G., S.T.K., O.Z., F.C., K.C., C.J.C., D.L.G. and K.L.S.

Writing, review, and/or revision of the manuscript: C.G. S.T.K., D.L.G. and K.L.S.

Technical and material support: G.B.M.

Study Supervision: H.F., D.L.G. and K.L.S.

These authors contributed equally: Caitlin Grzeskowiak, Samrat T. Kundu.

These authors jointly supervised this work: Don L. Gibbons, Kenneth L. Scott.

Deceased: Kenneth L. Scott.

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.

D.L.G. is a Lee Clark Fellow of the University of Texas MD Anderson Cancer Center.

The authors declare no competing interests.

Subjects:

Research Funding:

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).

This project was also supported by the Cancer Target Discovery and Development Network grants U01CA168449 and U01CA217875 to H.F.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • GENE-EXPRESSION SIGNATURE
  • CHROMATIN REMODELING COMPLEX
  • PROTEIN-PROTEIN INTERACTIONS
  • ANAPLASTIC LYMPHOMA KINASE
  • C-MYC
  • K-RAS
  • PANCREATIC-CANCER
  • MI-2/NURD COMPLEX
  • GROWTH-FACTOR
  • MOUSE MODEL

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

Show all authors Show less authors

Journal Title:

Nature Communications

Volume:

Volume 9, Number 1

Publisher:

, Pages 2732-2732

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Author(s) 2018

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote