title: Regulation of cell migration via the EGFR signaling pathway in oral squamous cell carcinoma cells.
abstract: Cell migration potency is essential in cancer metastasis and is often regulated by extracellular stimuli. Oral squamous cell carcinoma cell lines include those that are sensitive, as well as resistant, to the effects of the epidermal growth factor receptor (EGFR) inhibitor cetuximab on cell migration. In the present study, the molecular differences in the EGFR response to cell migration between the SAS cetuximab-sensitive and HSC4 cetuximab-resistant cell lines was examined. Treatment with the EGFR inhibitors AG1478 and cetuximab reduced the migration potency of SAS cells, but not HSC4 cells. The migration of the two cell lines was inhibited under serum-free culture conditions, and the addition of EGF to the serum-free medium promoted the migration of SAS cells, but not HSC4 cells. In addition, SAS cell migration was reduced by the mitogen-activated protein kinase kinase and protein kinase B (Akt) inhibitors PD98059 and MK2206, whereas HSC4 cell migration was only inhibited by MK2206. EGF induced an increase in extracellular signal-regulated kinase phosphorylation levels in HSC4 cells, and stimulated Akt phosphorylation levels in SAS cells. Furthermore, the staining of actin filaments with phalloidin was significantly increased by the inhibition of EGFR in SAS cells, but was not observed as altered in HSC4 cells. Conversely, the addition of EGF to the culture medium decreased the accumulation of actin filaments in SAS cells. The results suggest that the EGF-EGFR signaling pathway has an important role in SAS cell migration via the modulation of actin dynamics, and that HSC4 cell migration is regulated by a serum component other than EGFR.
authors.affiliation: Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohnishi
authors.affiliation: Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kakudo
authors.affiliation: Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nozaki
keywords: AG1478; EGF; EGFR; MK2206; PD98059; cetuximab