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  • Oncogenomics
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Identification of a metastasis signature and the DLX4 homeobox protein as a regulator of metastasis by combined transcriptome approach

Oncogene volume 26, pages 4600–4608 (2007)Cite this article

Abstract

Although widespread metastasis is the major cause of human lung cancer-related deaths, its underlying mechanism remains largely unclear. Our genome-wide comparison of the expression profiles of a highly metastatic lung cancer cell line, NCI-H460-LNM35 (LNM35), and its parental clone, NCI-H460-N15 (N15), resulted in the identification of a cancer metastasis signature composed of 45 genes. Through gene ontology analysis, our study also provided insights into how this 45-gene metastasis signature may contribute to the acquisition of metastatic potential. By applying the signature to datasets of human cancer cases, we could demonstrate significant associations with a subset of cases with poor prognosis not only for the two datasets of cancers of the lung but also for cancers of the breast. Furthermore, we were able to show that enforced expression of the DLX4 homeobox gene, which was identified as a gene with significant downregulation in LNM35 as well as with significant association with favorable prognosis for lung cancer patients, markedly inhibited in vitro motility and invasion as well as in vivo metastasis via both hematogenous and lymphogenous routes. Taken together, these findings indicate that our combined transcriptome analysis is an efficient approach in the search for genes possessing both clinical usefulness in terms of prognostic prediction in human cancer cases and clear functional relevance for studying cancer biology in relation to metastasis.

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Acknowledgements

We thank Keishi Katoh for his helpful discussion on bioinformatic analysis. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a Grain-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science.

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Author notes

  1. S Tomida and K Yanagisawa: These two authors contributed equally to this work. The microarray data were deposited in GEO (GSE4705 and GSE4716).

Authors and Affiliations

  1. Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya,, Japan

    S Tomida, K Yanagisawa, K Koshikawa & T Takahashi

  2. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan

    Y Yatabe

  3. Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan

    T Mitsudomi

  4. Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan

    H Osada

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  1. S Tomida
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Correspondence to T Takahashi.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Tomida, S., Yanagisawa, K., Koshikawa, K. et al. Identification of a metastasis signature and the DLX4 homeobox protein as a regulator of metastasis by combined transcriptome approach. Oncogene 26, 4600–4608 (2007). https://doi.org/10.1038/sj.onc.1210242

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