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

  • 1,
  • 2,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
  • 1,
  • 3,
  • 4,
  • 4 and
  • 1, 2Email author
Contributed equally
Molecular Cytogenetics20147 (Suppl 1) :I9

https://doi.org/10.1186/1755-8166-7-S1-I9

  • Published:

Keywords

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

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.

Notes

Authors’ Affiliations

(1)
Proteomics and Structural Biology Unit, India
(2)
G.N.R. Knowledge Centre for Genome Informatics, CSIRInstitute of Genomics and Integrative Biology, Delhi, India
(3)
Animal House, CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India
(4)
Division of Lipid Science and Technology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India

Copyright

© Thakur et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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