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

Shuta Tomida, K. Yanagisawa, K. Koshikawa, Y. Yatabe, T. Mitsudomi, H. Osada, T. Takahashi

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4600-4608
Number of pages9
JournalOncogene
Volume26
Issue number31
DOIs
Publication statusPublished - Jul 5 2007
Externally publishedYes

Fingerprint

Homeodomain Proteins
Transcriptome
Lung Neoplasms
Neoplasm Metastasis
Genes
Neoplasms
Gene Ontology
Homeobox Genes
Gene Expression Profiling
Down-Regulation
Clone Cells
Genome
Breast Neoplasms
Cell Line

Keywords

  • DLX4
  • Expression profile
  • Gene ontology
  • Lung cancer
  • Metastasis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Identification of a metastasis signature and the DLX4 homeobox protein as a regulator of metastasis by combined transcriptome approach. / Tomida, Shuta; Yanagisawa, K.; Koshikawa, K.; Yatabe, Y.; Mitsudomi, T.; Osada, H.; Takahashi, T.

In: Oncogene, Vol. 26, No. 31, 05.07.2007, p. 4600-4608.

Research output: Contribution to journalArticle

Tomida, Shuta ; Yanagisawa, K. ; Koshikawa, K. ; Yatabe, Y. ; Mitsudomi, T. ; Osada, H. ; Takahashi, T. / Identification of a metastasis signature and the DLX4 homeobox protein as a regulator of metastasis by combined transcriptome approach. In: Oncogene. 2007 ; Vol. 26, No. 31. pp. 4600-4608.
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