The first 2 authors contributed equally to this article.
An E3 ubiquitin ligase: c-Cbl†
A new therapeutic target of lung cancer
Article first published online: 23 MAY 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 23, pages 5344–5350, 1 December 2011
How to Cite
Lo, F.-Y., Tan, Y.-H. C., Cheng, H.-C., Salgia, R. and Wang, Y.-C. (2011), An E3 ubiquitin ligase: c-Cbl. Cancer, 117: 5344–5350. doi: 10.1002/cncr.26153
- Issue published online: 18 NOV 2011
- Article first published online: 23 MAY 2011
- Manuscript Accepted: 28 FEB 2011
- Manuscript Revised: 29 JAN 2011
- Manuscript Received: 22 OCT 2010
- gene therapy
Casitas B-lineage lymphoma (Cbl) is an E3 ubiquitin ligase of many tyrosine kinase receptors. The authors previously detected c-Cbl mutation and low protein expression in non-small cell lung cancer (NSCLC). Therefore, it was hypothesized that overexpression of wild-type c-Cbl (c-Cbl WT) exhibits tumor growth inhibition.
Wound healing and transwell assays were conducted to examine cell motility after c-Cbl WT transfection in NSCLC cell lines. The cell cycle was investigated by flow cytometry. A549 and H1299-Luc c-Cbl WT-transfected xenografts and experimental metastasis models were performed to investigate tumor growth and metastasis inhibition in vivo.
Wound healing and transwell assays demonstrated inhibition of migration in the A549 and H226br cells 4 to 24 hours after transfection. Ectopic c-Cbl WT expression was found to reduce cell proliferation at 48 hours in A549 cells. It is important to note that A549 and H1299-Luc cells with ectopic c-Cbl WT expression demonstrated inhibition of tumor growth in vivo. A549 cells overexpressing c-Cbl WT inhibited tumor metastasis in animal models.
To the best of the authors' knowledge, the current study is the first to demonstrate that c-Cbl WT protein overexpression inhibits tumor metastasis and tumor growth in lung cancer xenograft models. These results provide evidence that ectopic expression of c-Cbl WT protein can be potentially applied as targeted therapy for the treatment of lung cancer. Cancer 2011;. © 2011 American Cancer Society.