Journal
CANCER SCIENCE
Volume 102, Issue 8, Pages 1493-1500Publisher
WILEY
DOI: 10.1111/j.1349-7006.2011.01973.x
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science [20590919, 20590918, 21390257]
- Japan's Ministry of Education, Culture, Sports, Science and Technology
- US National Cancer Institute [P50CA70907]
- Department of defense (DOD)
- Ono Pharm. Cop.
- Boehringer-Ingelheim Cop.
- MDS
- Astellas Co.
- Novartis Phar. K.K.
- Pfizer Co.
- Shionogi Co.
- Chugai Co.
- NCI [P50CA70907]
- Grants-in-Aid for Scientific Research [23591145, 20590919, 23591144, 21390257, 20590918] Funding Source: KAKEN
Ask authors/readers for more resources
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. (Cancer Sci 2011; 102: 1493-1500)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available