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

Cleo E. Rolle, Yi Hung Carol Tan, Tanguy Y. Seiwert, Sapana Vora, Rajani Kanteti, Rifat Hasina, George B. Carey, Mosmi Surati, Ralph R. Weichselbaum, Mark W. Lingen, Everett E. Vokes, Ravi Salgia

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18726-18734
Number of pages9
JournalOncotarget
Volume8
Issue number12
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Keywords

  • Head and neck cancer
  • MET
  • c-CBL

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Rolle, C. E., Tan, Y. H. C., Seiwert, T. Y., Vora, S., Kanteti, R., Hasina, R., Carey, G. B., Surati, M., Weichselbaum, R. R., Lingen, M. W., Vokes, E. E., & Salgia, R. (2017). Expression and mutational analysis of c-CBL and its relationship to the MET receptor in head and neck squamous cell carcinoma. Oncotarget, 8(12), 18726-18734. https://doi.org/10.18632/oncotarget.9640