title: An E3 ubiquitin ligase: c-Cbl: a new therapeutic target of lung cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Fang-Yi
authors: FY
authors: Lo
authors: Yi-Hung Carol
authors: YH
authors: Tan
authors: Hung-Chi
authors: HC
authors: Cheng
authors: Ravi
authors: R
authors: Salgia
authors: Yi-Ching
authors: YC
authors: Wang
references: Oncogene. 2007 Oct 25;26(49):6968-78
references: 17486068
references: Nature. 2009 Aug 13;460(7257):904-8
references: 19620960
references: J Biol Chem. 2003 Jul 4;278(27):24600-7
references: 12716896
references: Blood. 2007 Aug 1;110(3):1004-12
references: 17446348
references: Mol Cell. 2001 Nov;8(5):995-1004
references: 11741535
references: PLoS One. 2010 Jan 29;5(1):e8972
references: 20126411
references: Ann Hematol. 2010 Jul;89(7):643-52
references: 20195608
references: J Cell Physiol. 2006 Oct;209(1):21-43
references: 16741904
references: Mol Cell Biol. 2008 May;28(9):3020-37
references: 18316398
references: Cancer Res. 2010 Feb 1;70(3):1141-53
references: 20086179
references: Science. 1999 Oct 8;286(5438):309-12
references: 10514377
references: Oncogene. 2008 Feb 7;27(7):957-65
references: 17653080
references: Br J Cancer. 2008 Sep 16;99(6):911-22
references: 19238632