Pivotal role of epithelial cell adhesion molecule in the survival of lung cancer cells

Tetsunari Hase, Mitsuo Sato, Kenya Yoshida, Luc Girard, Yoshihiro Takeyama, Mihoko Horio, Momen Elshazley, Tomoyo Oguri, Yoshitaka Sekido, David S. Shames, Adi F. Gazdar, John D. Minna, Masashi Kondo, Yoshinori Hasegawa

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of human cancers including lung cancer, and its contribution to increased proliferation through upregulation of cell cycle accelerators such as cyclins A and E has been well established in breast and gastric cancers. Nevertheless, very little is known about its role in supporting the survival of cancer cells. In addition, the functional role of EpCAM in the pathogenesis of lung cancer remains to be explored. In this study, we show that RNAi-mediated knockdown of EpCAM suppresses proliferation and clonogenic growth of three EpCAM-expressing lung cancer cell lines (H3255, H358, and HCC827), but does not induce cell cycle arrest in any of these. In addition, EpCAM knockdown inhibits invasion in the highly invasive H358 but not in less invasive H3255 cells in a Transwell assay. Of note, the EpCAM knockdown induces massive apoptosis in the three cell lines as well as in another EpCAM-expressing lung cancer cell line, HCC2279, but to a much lesser extent in a cdk4/hTERT immortalized normal human bronchial epithelial cell line, HBEC4, suggesting that EpCAM could be a therapeutic target for lung cancer. Finally, EpCAM knockdown partially restores contact inhibition in HCC827, in association with p27Kip1 upregulation. These results indicate that EpCAM could contribute substantially to the pathogenesis of lung cancer, especially cancer cell survival, and suggest that EpCAM targeted therapy for lung cancer may have potential.

Original languageEnglish
Pages (from-to)1493-1500
Number of pages8
JournalCancer science
Volume102
Issue number8
DOIs
Publication statusPublished - 08-2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Pivotal role of epithelial cell adhesion molecule in the survival of lung cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Hase, T., Sato, M., Yoshida, K., Girard, L., Takeyama, Y., Horio, M., Elshazley, M., Oguri, T., Sekido, Y., Shames, D. S., Gazdar, A. F., Minna, J. D., Kondo, M., & Hasegawa, Y. (2011). Pivotal role of epithelial cell adhesion molecule in the survival of lung cancer cells. Cancer science, 102(8), 1493-1500. https://doi.org/10.1111/j.1349-7006.2011.01973.x