Synergistic cooperation of EGFR / Stat 3 / Smad 3 axis induces human nasopharyngeal carcinoma cells apoptosis

Tumor growth factors-β (TGF-β) signaling is associated with regulation in various types of cancer cells apoptosis. Epidermal growth factor receptor (EGFR) signaling is involved in the progression of human nasopharyngeal carcinoma (NPC). Whether there is a crosstalk between TGF-β and EGFR signaling that regulating NPC cells apoptosis remains unclear. Here, we report agonist-mediated TGF-β signaling activation induced Smad2/3 phosphorylation leading to human NPC CNE1 cells apoptosis in vitro. Antagonist-mediated EGFR inhibition synergistically promotes TGF-β activation-induced CNE1 cells apoptosis. Inhibition of EGFR expression by siRNA led a reduction on Stat3 phosphorylation, which results in over expression of TGF-β-activated Smad3 phosphorylation in CNE1 cells. These results show that EGFR inhibition synergistically promotes TGF-β-induced human NPC cells apoptosis through EGFR/Stat3/Smad3 Signaling cooperation. The novel molecular network potentially gives insights to the moleculartargeted therapeutics development for human nasopharyngeal carcinoma.