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

// Cleo E. Rolle 1, * , Yi-Hung Carol Tan 1, * , Tanguy Y. Seiwert 1 , Sapana Vora 2 , Rajani Kanteti 1 , Rifat Hasina 1 , George B. Carey 1 , Mosmi Surati 3 , Ralph R. Weichselbaum 4 , Mark W. Lingen 5 , Everett E. Vokes 1 , Ravi Salgia 6 1 Department of Medicine, The University of Chicago, Chicago, IL, USA 2 Department of Pediatrics, The University of Chicago, Chicago, IL, USA 3 Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA 4 Department of Radiation and Cellular Oncology/Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA 5 Department of Pathology, The University of Chicago, Chicago, IL, USA 6 Department of Medical Oncology and Therapeutic Research, City of Hope, Duarte, CA, USA * These authors have contributed equally to this work Correspondence to: Ravi Salgia, email: rsalgia@coh.org Keywords: c-CBL, MET, head and neck cancer Received: October 01, 2015     Accepted: April 16, 2016     Published: May 26, 2016 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.