The mechanism of action of NME2, a widely accepted metastasis-suppressor gene, is poorly understood. Recently we found that NME2 directly regulates transcription of the c-MYC proto-oncogene. This prompted a genome-wide study to ascertain whether NME2 exerts its anti-metastatic action through transcriptional regulation. Chromatin-immunoprecipitation followed by massively parallel sequencing (ChIPseq) along with transcriptome profiling uncovered a network of genes involved in intercellular contact, focal adhesion and actin assembly under direct transcriptional control of NME2. In line with this, NME2-depleted cells displayed increased focal adhesion points and altered actin stress fiber organization. Our findings demonstrate that NME2 regulates transcription of a key focal adhesion factor vinculin and its localization within adhesion foci. NME2-depleted A549 lung cancer cells showed higher invasiveness in vitro and seeded more metastases in vivo. Consistent with these findings, expression of several NME2-transcriptional target genes related closely to advanced tumor stages with metastatic proclivity, and NME2 levels predicted patient survival.
Author information
Authors and Affiliations
Corresponding author
Additional information
Ram Krishna Thakur, Vinod Kumar Yadav, Akinchan Kumar contributed equally to this work.
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Thakur, R.K., Yadav, V., Kumar, A. et al. Functional genomics of lung cancer progression reveals mechanism of metastasis suppressor function. Mol Cytogenet 7 (Suppl 1), I9 (2014). https://doi.org/10.1186/1755-8166-7-S1-I9
Published:
DOI: https://doi.org/10.1186/1755-8166-7-S1-I9