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EMX2 is epigenetically silenced and suppresses growth in human lung cancer

Oncogene volume 29, pages 5969–5975 (2010)Cite this article

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A Corrigendum to this article was published on 04 November 2010

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.

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Acknowledgements

This study was supported by grant from Joan’s Legacy: uniting against Lung Cancer Research Grant, NIH/NCI grant R01CA125030 and the Eileen D Ludwig endowed for Thoracic Oncology Research (to BH); the Bonnie J Addario Lung Cancer Foundation, the Kazan, McClain, Abrams, Fernandez, Lyons, Greenwood, Harley and Oberman Foundation and the Barbara Isackson Lung Cancer Research Fund (DJ); Swedish Cancer Institute (MJ); NIH/NCI grants R01CA130980, R01CA13256 and DOD BCRP Era of Hope Scholar Award (W81XWH-06-1-0416) (to LMC). Microarray profiling was done by the UCSF Shared Microarray Core Facilities. We thank M Roshni Ray for editing this paper.

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Author notes

  1. J Okamoto and T Hirata: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Thoracic Oncology Program, University of California, San Francisco, CA, USA

    J Okamoto, T Hirata, Z Chen, I Mikami, H Li, A Beltran, G Clement, Y Shi, F Zhang, D Jablons & B He

  2. Department of Surgery, Division of Thoracic Surgery, Nippon Medical School, Tokyo, Japan

    J Okamoto, T Hirata, I Mikami, K Koizumi & K Shimizu

  3. Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China

    Z Chen & H-M Zhou

  4. Department of Pathology, University of California, San Francisco, CA, USA

    M Johansson & L M Coussens

  5. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA

    M Johansson, L M Coussens, D Jablons & B He

  6. Biosciences Division, SRI International, Menlo Park, CA, USA

    Y Shi

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  1. J Okamoto
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Correspondence to B He.

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Okamoto, J., Hirata, T., Chen, Z. et al. EMX2 is epigenetically silenced and suppresses growth in human lung cancer. Oncogene 29, 5969–5975 (2010). https://doi.org/10.1038/onc.2010.330

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