RNA-binding protein-regulated fibronectin is essential for EGFR-activated metastasis of head and neck squamous cell carcinoma

Jiunn Min Shieh, Ting Wei Chang, Jing He Wang, Song Ping Liang, Pei Lu Kao, Liang Yi Chen, Chia Jui Yen, Yun Ju Chen, Wen Chang Chang, Ben Kuen Chen

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

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 role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5′ untranslated region (5′-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells’ attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.

原文English
文章編號e23206
期刊FASEB Journal
37
發行號10
DOIs
出版狀態Published - 2023 10月

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 生物化學
  • 分子生物學
  • 遺傳學

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