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

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.

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Correspondence to Shantanu Chowdhury.

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Ram Krishna Thakur, Vinod Kumar Yadav, Akinchan Kumar contributed equally to this work.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated.

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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).

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  • Advanced Tumor Stage
  • Metastasis Suppressor
  • Actin Stress Fiber
  • A549 Lung
  • Intercellular Contact