Transforming growth factorβ1 transactivates EGFR via an H2O2-dependent mechanism in squamous carcinoma cell line

TGFβ is known to transactivate EGFR. However, the signaling component involved in this crosstalk has yet to be revealed. Here, we found that TGFβ1 phosphorylated EGFR in a dose-dependent manner in SCC13 and A431 cells, and it was not blocked by EGF-neutralizing antibody. H2O2 was increased by TGFβ1 treatment in the same time-kinetics as EGFR activation. Pretreatment of N-acetyl cysteine abolished TGFβ1-induced H2O2 induction and EGFR activation. Direct treatment of H2O2 phosphorylated EGFR and catalase inhibitor prolonged TGFβ1-induced EGFR activation. These results show that TGFβ1 activates EGFR via an H2O2-dependent mechanism, which subsequently leads to the activation of Erk1/2.