LPAR3 and COL8A1, as matrix stiffness-related biomarkers, promote nasopharyngeal carcinoma metastasis by triggering EMT and angiogenesis

Abstract

Matrix stiffness affects the progression of nasopharyngeal carcinoma, but the underlying mechanism is still unknown. Here, we demonstrated that nasopharyngeal carcinoma tissues with distant metastasis contain large collagen deposits and strong matrix stiffness. First, we performed RNA-seq analysis of nasopharyngeal carcinoma cells cultured on polyacrylamide hydrogel systems and found that LPAR3 and COL8A1 are potential matrix stiffness markers. Based on in vivo and in vitro experiments, matrix stiffness mainly affected tumor metastasis rather than proliferation. Subsequently, we found that matrix stiffness triggers the formation of epithelial-mesenchymal transition by increasing the expression of LPAR3 in nasopharyngeal carcinoma, which is related to metastasis. In addition, matrix stiffness promotes the expression of COL8A1 secreted by nasopharyngeal carcinoma and is related to tumor angiogenesis. Simultaneous inhibition of LPAR3 and COL8A1 genes significantly reduced nasopharyngeal carcinoma invasion and metastasis. Based on the investigation, we confirmed that matrix stiffness governs the progression of nasopharyngeal carcinoma and that LPAR3 and COL8A1, as matrix stiffness related biomarkers, promote nasopharyngeal carcinoma metastasis by inducing epithelial-mesenchymal transition and angiogenesis. Overall, the in-depth exploration of matrix stiffness may provide a strategy for clinical treatment intervention and provide promising targets for clinical nasopharyngeal carcinoma treatment.