Interplay between the NF-κB and hedgehog signaling pathways predicts prognosis in esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy

Abstract

Tumor recurrence and metastasis in esophageal squamous cell carcinoma (ESCC ) are primary causes of patient mortality. The nuclear factor (NF)-κB signaling pathway and hedgehog signaling pathway were previously reported to contribute to cell growth and metastasis in ESCC . The present study therefore investigated the roles of the NF-κB and hedgehog pathways in ESCC tumors following neoadjuvant chemoradiotherapy (NCRT). By immunohistochemistry staining, it was observed that NF-κB and glioma-associated oncogene homolog 1 (Gli1), key components of the NF-κB and hedgehog pathways, respectively, were decreased following NCRT, which was further confirmed by western blotting and reverse transcription-quantitative polymerase chain reaction analysis. In addition, survival analysis suggested that high expression levels of either NF-κB or Gli1 were associated with poor overall survival (OS) of patients. In the esophageal cell line TE-8, NF-κB and Gli1 formed a positive feedback loop, and inhibition of either NF-κB or Gli1 may inhibit cell migration, invasion and proliferation. The results of the present study demonstrated that activation of the NF-κB and hedgehog signaling pathways limited the OS of patients with ESCC following NCRT, and may therefore be suitable targets for ESCC treatment.