WISP-1 Promotes Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells via the miR-153-3p/Snail Axis

Abstract

Around half of all patients with oral squamous cell carcinoma (OSCC) present with lymphatic metastasis, a strong predictor of poor survival. Improving survival rates depends on preventing the first step in the "invasion<b>-</b>metastasis cascade," epithelial<b>-</b>to<b>-</b>mesenchymal transition (EMT), and developing antilymphangiogenesis therapies that antagonize lymphatic metastasis. The extracellular matrix<b>-</b>related protein WISP<b>-</b>1 (WNT1<b>-</b>inducible signaling pathway protein<b>-</b>1) stimulates bone remodeling and tumor progression. We have previously reported that WISP<b>-</b>1 promotes OSCC cell migration and lymphangiogenesis induced by vascular endothelial growth factor C (VEGF<b>-</b>C). This investigation sought to determine the role of WISP<b>-</b>1 in regulating EMT in OSCC. Our analysis of oral cancer data from The Cancer Genome Atlas (TCGA) database revealed significant and positive associations between levels of WISP<b>-</b>1 expression and clinical disease stage, as well as regional lymph node metastasis. We also found higher levels of WISP<b>-</b>1 expression in serum samples obtained from patients with OSCC compared with samples from healthy controls. In a series of in vitro investigations, WISP<b>-</b>1 activated EMT signaling via the FAK/ILK/Akt and Snail signaling transduction pathways and downregulated miR<b>-</b>153<b>-</b>3p expression in OSCC cells. Our findings detail how WISP<b>-</b>1 promotes EMT via the miR<b>-</b>153<b>-</b>3p/Snail axis in OSCC cells.