Open AccessExpression and mutational analysis of c-CBL and its relationship to the MET receptor in head and neck squamous cell carcinoma
Author(s) -
Cleo E. Rolle,
YiHung 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
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.9640
Subject(s) - head and neck squamous cell carcinoma , medicine , oncology , metastasis , cancer research , cancer , cd44 , head and neck cancer , biology , cell , genetics
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.