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.
Functional genomics of lung cancer progression reveals mechanism of metastasis suppressor function
Vinod Kumar Yadav
Pankaj Kumar
MJ Mahesh Kumar
Krishnendu Pal
Rajkumar Banerjee
Shantanu Chowdhury
Corresponding author.
Contributed equally.
Supplement
Proceedings of the International Conference on Human Genetics and 39th Annual Meeting of Indian Society of Human Genetics
The conference and publication charges for this supplement were funded through the co-sponsorship of the Gujarat State Biotechnology Mission (GSBTM) and Department of Science and Technology (DST), Government of Gujarat, Genzyme and Zydus Cadila. Genzyme and Zydus Cadila were not involved in the selection of abstracts.
Conference
23-25 January 2014
International Conference on Human Genetics and 39th Annual Meeting of the Indian Society of Human Genetics (ISHG)
Ahmedabad, India
Collection date 2014.
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