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Updated: Feb 7, 2026
Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment
Published on: February 3, 2016
In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer
Caitlin L Grzeskowiak1, Samrat T Kundu2, Xiulei Mo3
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
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.
Insights
Researchers identified 28 genes promoting lung cancer metastasis in a KRAS-mutant mouse model. One gene, GATAD2B, drives tumor growth and spread by interacting with the c-MYC pathway.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Targeting genetic aberrations is crucial for precision oncology in lung cancer.
- KRAS mutations are common drivers of lung adenocarcinoma, but associated pro-metastatic genes are not well understood.
Purpose of the Study:
- To identify genes that promote tumor metastasis in KRAS-mutant lung adenocarcinoma.
- To investigate the KRAS-dependence of these identified genes.
- To elucidate the mechanistic role of GATAD2B in KRAS-mutant lung cancer.
Main Methods:
- In vivo functional screen of 217 genetic aberrations in a KRAS-mutant lung adenocarcinoma mouse model.
- Utilized a human lung cell model with a regulatable mutant KRAS allele.
- Employed a lentiviral system for in vivo activation of mutant KRAS and gene co-expression in mice.
Main Results:
- Identified 28 genes that significantly promoted lung metastasis in mice.
- Confirmed KRAS-dependence for several identified genes using human cell models and in vivo systems.
- Mechanistic studies revealed GATAD2B as a dual-activity gene promoting tumorigenesis and metastasis via c-MYC pathway hyperactivation.
Conclusions:
- This study identified novel genetic drivers of metastasis in KRAS-mutant lung cancer.
- GATAD2B is a key mediator of both tumor growth and metastasis in this context.
- Findings offer potential new therapeutic targets for precision oncology in KRAS-mutant lung adenocarcinoma.
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