Epidermal growth factor stimulates STAT5 via EGFR to promote lung adenocarcinoma growth

Abstract Background/aim Activation of the epidermal growth factor receptor (EGFR) by its ligand, epidermal growth factor (EGF), initiates multiple signaling cascades that enhance tumor cell growth and survival. Although STAT5 has been implicated in oncogenic processes, its contribution to EGFR-mediated lung adenocarcinoma remains poorly defined. This study aimed to clarify the role of EGF-driven STAT5 activation through EGFR in regulating the proliferation of lung adenocarcinoma cells. Materials and methods Human lung adenocarcinoma cell lines (A549 and H441) were exposed to different concentrations of EGF across a range of time intervals. STAT5 phosphorylation and nuclear localization were examined by western blotting and immunofluorescence microscopy. Proliferative capacity was assessed using cell viability assays, while siRNA-mediated silencing of EGFR was employed to determine the dependence of STAT5 activation on receptor signaling. Results EGF stimulation markedly enhanced STAT5 phosphorylation at Tyr694 in a concentration- and time-dependent manner. Immunofluorescence confirmed that phosphorylated STAT5 accumulated in the nucleus, consistent with transcriptional activity. Suppression of EGFR significantly diminished EGF-induced STAT5 activation, establishing EGFR as an essential upstream regulator. Moreover, pharmacologic inhibition of STAT5 substantially reduced EGF-driven proliferation, underscoring the functional relevance of this pathway. Conclusion These findings identify the EGFR–STAT5 signaling axis as a key contributor to lung adenocarcinoma proliferation. Therapeutic strategies that disrupt this pathway may represent an effective approach to suppress tumor growth and complement existing EGFR-targeted treatments.