RRC ID 61824
Author Yasui H, Ohnishi Y, Nakajima M, Nozaki M.
Title Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation.
Journal Oncol Rep
Abstract The activation of receptor tyrosine kinases (RTKs) results in cellular effects including cell proliferation, survival, migration and invasion; RTKs also play an important role in tumourigenesis. It has been reported that EGFR signalling controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells but not of HSC4 cells, although the proliferation of HSC4 cells is regulated by EGF/EGFR. In the present study, we investigated the roles of EGFR and the c-Met signalling pathway in cell migration via filopodia and lamellipodia formation, which may be prerequisites for migration. To explore the role of c-Met in cell migration, we inhibited c-Met RTK activity using the c-Met inhibitor SU11274 and activated c-Met using hepatocyte growth factor (HGF) in three OSCC cell lines HSC4, SAS and Ca9-22 and investigated migration potency using a wound healing assay. We showed that inhibition of c-Met significantly suppressed, and activation of c-Met significantly promoted, the migration of OSCC cells. Additionally, the migration of SAS and Ca9-22 cells was inhibited by the EGFR inhibitors AG1478 and cetuximab and promoted by EGF treatment. Moreover, migration potency was correlated with lamellipodia formation. Furthermore, western blot analyses demonstrated that SU11274 decreased and HGF increased lamellipodin protein levels as well as phosphorylated c-Met levels. Collectively, we demonstrated that c-Met signalling induced lamellipodia formation by upregulating lamellipodin, thereby promoting the migration of OSCC cells.
Volume 37(6)
Pages 3674-3680
Published 2017-6-1
DOI 10.3892/or.2017.5587
PMID 28440510
MeSH Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Movement / drug effects Cell Movement / genetics Cell Proliferation / drug effects Cetuximab / administration & dosage Epidermal Growth Factor / genetics Epidermal Growth Factor / metabolism ErbB Receptors / antagonists & inhibitors ErbB Receptors / genetics* Hepatocyte Growth Factor / genetics Hepatocyte Growth Factor / metabolism Humans Indoles / administration & dosage Mouth Neoplasms / drug therapy* Mouth Neoplasms / genetics Mouth Neoplasms / pathology Phosphatidylinositol 3-Kinases / genetics Piperazines / administration & dosage Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-met / antagonists & inhibitors Proto-Oncogene Proteins c-met / genetics* Pseudopodia / drug effects Pseudopodia / genetics Quinazolines / administration & dosage Signal Transduction / drug effects Sulfonamides / administration & dosage Tyrphostins / administration & dosage
IF 3.417
Human and Animal Cells HSC-4(RCB1902) SAS(RCB1974) Ca9-22(RCB1976)