Phosphorylation of STAT3 in head and neck cancer requires p38 MAPKinase, whereas phosphorylation of STAT1 occurs via a different signaling pathway.

STAT proteins work as signal transducers as well as transcription and activator proteins. In head and neck cancer both STAT1 and STAT3 are overexpressed. STAT3 contributes to malignant transformation and regulates tumor promoting cytokines, whereas STAT1 is purported to act antagonistically as a tumor suppressor. Since our previous data determined p38 MAPK to be a potent regulator of interleukin-6 (IL-6) and IL-8 expression in permanent head and neck squamous cell carcinoma (HNSCC) cell lines, we investigated the influence of this pathway on STAT3 and STAT1. Down-regulation of p38 MAPK expression levels by siRNA strongly reduces phosphorylation of STAT3 tyrosine 705 without any effects on phosphorylation of STAT3 serine 727 and STAT1. Analyzing the effect of silencing of ERK1/2 MAPK revealed that this MAPK strongly influences IL-6 and IL-8 expression, but is not involved in either activation of STAT1 or STAT3. Our data indicate STAT3 as a potent promoter of HNSCC progression.