Abstract
Study of the c-Met-HGF axis in non-small cell lung cancer (NSCLC) has focused on the roles of c-MET signaling in neoplastic epithelial cells and the secretion of its ligand hepatocyte growth factor (HGF) by tumor stromal cells. However, there is increasing evidence that some leukocyte sub-sets also express c-MET raising the possibility of an immunomodulatory role for this axis. Consequently, the role of the c-MET- HGF axis in immunoncology is an active area of ongoing research. This review summarizes current knowledge of c-MET expression in NSCLC, the prognostic significance of these findings and the mechanisms by which the c-MET-HGF axis might act in NSCLC, focusing on the emerging evidence for an immunoregulatory role.
Highlights
NON-IMMUNOLOGICAL ROLES FOR THE c-MET-hepatocyte growth factor (HGF) AXIS IN NON-SMALL CELL LUNG CANCER c-MET is a tyrosine kinase receptor with an extracellular α-chain and a transmembrane β-chain joined by disulphide bonds
This review summarizes current knowledge of c-MET expression in non-small cell lung cancer (NSCLC), the prognostic significance of these findings and the mechanisms by which the c-MET-HGF axis might act in NSCLC, focusing on the emerging evidence for an immunoregulatory role
In addition selective inhibition or SiRNA knockdown of c-MET decreased the viability of non-small cell lung cancer (NSCLC) cells demonstrating the direct effects of c-MET in promoting tumor growth [7]
Summary
NON-IMMUNOLOGICAL ROLES FOR THE c-MET-HGF AXIS IN NON-SMALL CELL LUNG CANCER c-MET is a tyrosine kinase receptor with an extracellular α-chain and a transmembrane β-chain joined by disulphide bonds. In lung adenocarcinomas various missense mutations and alternatively spliced products have been identified These include Exon-14 splice mutations that result in reduced receptor degradation and prolonged activation of the c-MET receptor, and have been reported to occur in 3% of lung adenocarcinoma and 2.3% other lung tumors [8]. Immunological Roles for MET-HGF in NSCLC selected reports of clinical responses to c-MET inhibitors in clinical settings in patients with splice mutations or amplification of the c-MET receptor [8,9,10,11]. The association between tumor production of HGF and NSCLC survival is summarized (Table 1) These observational studies are limited in their conclusions due to their retrospective nature and it is difficult to directly compare the different methodologies used, these studies highlight that there may be a trend toward increased c-MET
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
