title: Pivotal role of epithelial cell adhesion molecule in the survival of lung cancer cells.
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 p27(Kip1) 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.
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Hase
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sato
authors.forename: Kenya
authors.initials: K
authors.lastname: Yoshida
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeyama
authors.forename: Mihoko
authors.initials: M
authors.lastname: Horio
authors.forename: Momen
authors.initials: M
authors.lastname: Elshazley
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Oguri
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
authors.forename: David S
authors.initials: DS
authors.lastname: Shames
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology; D000071858:Epithelial Cell Adhesion Molecule; D016193:G1 Phase; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000473:pathology*; D009361:Neoplasm Invasiveness
chemical_list: D000951:Antigens, Neoplasm; C436291:CDKN1B protein, human; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D050760:Cyclin-Dependent Kinase Inhibitor p27