Abstract 3607: RNA-binding proteins are essential for EGF-induced fibronectin expression and metastasis of head and neck squamous cell carcinoma

Abstract

Abstract There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the precise mechanism involved in modulating EGF-associated metastasis in HNSCC remains unclear. In this study, we reveal that the concurrent expression of EGFR and fibronectin (FN1) was highly associated with the stages of HNSCC progression. EGF-induced fibronectin/integrin axis enhanced tumor-endothelial cell interaction and increased endothelial permeability, conferred HNSCC cell metastasis. Mechanistically, we found that ERK and NF-κB pathway activation was essential for EGF-induced fibronectin expression. In addition, EGF-enhanced mRNA stability of fibronectin occurred through the 5’ untranslated region (5’-UTR) of the gene and was mediated by nucleolin (NCL) and hnRNPA2/B1, which were also involved in the regulation of epithelial-mesenchymal transition gene expression. Intriguingly, the in vivo study showed that depletion of NCL, hnRNPA2/B1, and inhibition of the fibronectin/integrin axis significantly inhibited EGF-promoted HNSCC metastasis in the lung. Our data suggests that the nucleolin/hnRNPA2/B1-regulated fibronectin is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis. Citation Format: Ting-Wei Chang, Wen-Chang Chang, Ben-Kuen Chen. RNA-binding proteins are essential for EGF-induced fibronectin expression and metastasis of head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3607.