Expression and mutational analysis of c-CBL and its relationship to the MET receptor in head and neck squamous cell carcinoma

Oncotarget. 2017 Mar 21;8(12):18726-18734. doi: 10.18632/oncotarget.9640.


MET is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and degraded by c-CBL E3-ubiquitin ligase. We investigated genetic variations of c-CBL in HNSCC and the relationship between c-CBL and MET expression. High MET, low c-CBL expression was detected in 10 cell lines and 73 tumor tissues. Two novel mutations (L254S, L281F), and the single nucleotide polymorphism (SNP) P782L were identified from archival tumor tissues. 27.3% of loss of heterozygosity was found at CBL locus. Ectopic expression of wild-type c-CBL in SCC-35 cells downregulated MET expression and decreased cell viability. These results suggest MET overexpression is related to altered c-CBL expression, which may influence tumorigenesis.

Keywords: MET; c-CBL; head and neck cancer.

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • DNA Mutational Analysis
  • Gene Expression Regulation, Neoplastic / genetics*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Loss of Heterozygosity
  • Proto-Oncogene Proteins c-cbl / genetics*
  • Proto-Oncogene Proteins c-met / genetics*
  • Squamous Cell Carcinoma of Head and Neck
  • Tissue Array Analysis


  • Proto-Oncogene Proteins c-cbl
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • CBL protein, human