Regulation of cell migration via the EGFR signaling pathway in oral squamous cell carcinoma cells

Abstract

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.

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

“…20,32,33 Further, the results revealed stiffening of cancer cells on the stiff substrate which was measured by the AFM. 36 The results showed that Cetuximab treatment led to a 25 and 33% increase in the cellular stiffness of MCF7 and MDA-MB-231 cells, respectively. [14][15][16][17] These studies concluded that cells display reduced stiffness on soft substrates.…”

Molecular Basis of Modern Targeted Therapy for Squamous Cell Carcinoma of the Tongue and Oral Mucosa With Monoclonal Antibodies

“…По своим функциям ERBB1 сходен с ERBB4, который ассоциируется с процессами дифференцировки эпителиальных клеток. В активированном димерном состоянии этот рецептор взаимодействует с адапторными белками Grb 2 и Shc, ак-тиватором транскрипции STAT5 и в отличие от ERBB1 способен активировать сигнальный каскад PI3K / Akt [15]. Рецептор ERBB3 не является автономным членом семей-ства, но способен самоассоциироваться в неактивные оли-гомеры, которые разрушаются при соединении рецептора с лигандом (неурегулином) [16].…”

Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation

“…Cell migration was determined using a scratch wound healing assay, as described elsewhere (18,19) with slight modifications. Briefly, semi-confluent cells in 12-well plates were treated with 10 µg/ml mitomycin C for 4 h to block proliferation.…”

“…The migration potency of HSC4 cells was induced by stimulation of an unknown factor in serum other than EGF (19).…”

“…Previously, we showed that EGFR inhibitors suppressed cell migration in OSCC SAS cells but not HSC4 cells (18,19). Another RTK involved in the regulation of motility is c-Met, activated by hepatocyte growth factor (HGF, also known as scatter factor) (20,21).…”