Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation

Abstract

The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells.

A Small Organic Molecule Blocks EGFR Transport into the Nucleus by the Nonclassical Pathway Resulting in Repression of Cancer Invasion

“…It has been reported that EGFR internalization is enhanced by ligand‐dependent and ‐independent activation of EGFR . Therefore, after we induced EGFR activation in cells upon treatment with 100 ng mL −1 EGF for 60 min, the binding affinities of activated EGFR with KPNB1 were examined by a pull‐down assay, as described in the Supporting Information.…”

“…It has been reportedt hat EGFR internalization is enhanced by ligand-dependenta nd -independent activation of EGFR. [27,28] Therefore, after we induced EGFR activation in cells upon treat-ment with 100 ng mL À1 EGF for 60 min, the binding affinitieso f activatedE GFR with KPNB1 were examined by ap ull-down assay,a sd escribed in the Supporting Information. Thus, His-KPNB1-loaded beads were incubated with EGF-treated cell lysates or untreated cell lysates,a nd eluted proteins were resolved on SDS-PAGE gels and stainedw ith KPNA, KPNB1, and EGFR antibodies.…”

Regulation of intestinal myofibroblasts by KRas-mutated colorectal cancer cells through heparin-binding epidermal growth factor-like growth factor

“…HB-EGF is an EGF-family molecule that regulates cell proliferation and differentiation (31). Moreover, in cancer progression, HB-EGF promotes tumor cell growth/survival and angiogenesis (31,37), whereas, HB-EGF promotes the migration of epithelial cells and fibroblasts (38)(39)(40). Herein, HB-EGF expression was upregulated in KRasV12-aMoC1 cells, and HB-EGF enhanced IMF migration (Fig.…”

Characterization of Neoplastic Cells in the Cystic Space of Invasive Micropapillary Carcinoma of the Canine Mammary Gland.

“…Immuno uorescence was performed for aSMA, Vimentin, CD31, Von Willebrand Factor, p63, S100A4, Lamin B1 or B2, and MUC1, as previously described in Rodrigues M.A. et al (2016) [20][21][22][23].…”