Functional genomics of lung cancer progression reveals mechanism of metastasis suppressor function

• Published in: Molecular cytogenetics 2014, Vol.7 (Suppl 1 Proceedings of the International Conference on Human), p.I9-I9, Article I9
• Main Authors: Thakur, Ram Krishna, Yadav, Vinod Kumar, Kumar, Akinchan, Basundra, Richa, Kar, Anirban, Halder, Rashi, Singh, Ankita, Kumar, Pankaj, Baral, Aradhita, Kumar, Mj Mahesh, Pal, Krishnendu, Banerjee, Rajkumar, Chowdhury, Shantanu
• Format: Article
• Language: English
• Subjects: Actin; Speaker Presentation
• ISSN: 1755-8166; 1755-8166
• DOI: 10.1186/1755-8166-7-S1-I9

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.