EMX2 is epigenetically silenced and suppresses growth in human lung cancer

J. Okamoto, T. Hirata, Z. Chen, H. M. Zhou, I. Mikami, H. Li, A. Beltran, M. Johansson, Lisa Coussens, G. Clement, Y. Shi, F. Zhang, K. Koizumi, K. Shimizu, D. Jablons, B. He

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Lung cancer is a common cancer and the leading cause of cancer-related death worldwide. Aberrant activation of WNT signaling is implicated in lung carcinogenesis. EMX2, a human homologue of the Drosophila empty spiracles gene is a homeodomain-containing transcription factor. The function of EMX2 has been linked to the WNT signaling pathway during embryonic patterning in mice. However, little is known about the role of EMX2 in human tumorigenesis. In this study, we found that EMX2 was dramatically downregulated in lung cancer tissue samples and this downregulation was associated with methylation of the EMX2 promoter. Restoration of EMX2 expression in lung cancer cells lacking endogenous EMX2 expression suppressed cell proliferation and invasive phenotypes, inhibited canonical WNT signaling, and sensitized lung cancer cells to the treatment of the chemo cytotoxic drug cisplatin. On the other hand, knockdown of EMX2 expression in lung cancer cells expressing endogenous EMX2 promoted cell proliferation, invasive phenotypes and canonical WNT signaling. Taken together, our study suggests that EMX2 may have important roles as a novel suppressor in human lung cancer.

Original languageEnglish (US)
Pages (from-to)5969-5975
Number of pages7
JournalOncogene
Volume29
Issue number44
DOIs
StatePublished - Nov 4 2010
Externally publishedYes

Fingerprint

Lung Neoplasms
Growth
Carcinogenesis
Down-Regulation
Cell Proliferation
Phenotype
Methylation
Cisplatin
Drosophila
Neoplasms
Transcription Factors
Lung
Pharmaceutical Preparations
Genes

Keywords

  • EMX2
  • lung cancer
  • methylation
  • tumor suppression
  • WNT signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Okamoto, J., Hirata, T., Chen, Z., Zhou, H. M., Mikami, I., Li, H., ... He, B. (2010). EMX2 is epigenetically silenced and suppresses growth in human lung cancer. Oncogene, 29(44), 5969-5975. https://doi.org/10.1038/onc.2010.330

EMX2 is epigenetically silenced and suppresses growth in human lung cancer. / Okamoto, J.; Hirata, T.; Chen, Z.; Zhou, H. M.; Mikami, I.; Li, H.; Beltran, A.; Johansson, M.; Coussens, Lisa; Clement, G.; Shi, Y.; Zhang, F.; Koizumi, K.; Shimizu, K.; Jablons, D.; He, B.

In: Oncogene, Vol. 29, No. 44, 04.11.2010, p. 5969-5975.

Research output: Contribution to journalArticle

Okamoto, J, Hirata, T, Chen, Z, Zhou, HM, Mikami, I, Li, H, Beltran, A, Johansson, M, Coussens, L, Clement, G, Shi, Y, Zhang, F, Koizumi, K, Shimizu, K, Jablons, D & He, B 2010, 'EMX2 is epigenetically silenced and suppresses growth in human lung cancer', Oncogene, vol. 29, no. 44, pp. 5969-5975. https://doi.org/10.1038/onc.2010.330
Okamoto J, Hirata T, Chen Z, Zhou HM, Mikami I, Li H et al. EMX2 is epigenetically silenced and suppresses growth in human lung cancer. Oncogene. 2010 Nov 4;29(44):5969-5975. https://doi.org/10.1038/onc.2010.330
Okamoto, J. ; Hirata, T. ; Chen, Z. ; Zhou, H. M. ; Mikami, I. ; Li, H. ; Beltran, A. ; Johansson, M. ; Coussens, Lisa ; Clement, G. ; Shi, Y. ; Zhang, F. ; Koizumi, K. ; Shimizu, K. ; Jablons, D. ; He, B. / EMX2 is epigenetically silenced and suppresses growth in human lung cancer. In: Oncogene. 2010 ; Vol. 29, No. 44. pp. 5969-5975.
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