LPAR3 and Col8A1, as matrix stiffness-related biomarkers, promote nasopharyngeal carcinoma metastasis by triggering epithelial-mesenchymal transition and angiogenesis

Abstract Matrix stiffness affects the progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism is still unknown. It has been demonstrated that the stiffness of collagen fibers deposited in NPC and adjacent tissues differs. Here, we performed RNA-seq analysis of NPC cells cultured on polyacrylamide (PA) hydrogel systems and found that LPAR3 and Col8A1 are potential matrix stiffness markers. Besides analyzing cells in vitro, a nude mouse model of tumorigenesis with NPC cells expressing low levels of LPAR3 and Col8A1 showed a reduction in tumorigenesis. We found that matrix stiffness triggers the formation of EMT by increasing the expression of LPAR3 in NPC, which is related to metastasis. In addition, matrix stiffness promotes the expression of Col8A1 secreted by NPC and is related to tumor angiogenesis. Simultaneous inhibition of LPAR3 and Col8A1 genes significantly reduced NPC invasion and metastasis. Based on our investigation, there is no doubt that matrix stiffness governs the progression of NPC, and that LPAR3 and Col8A1 can be used as matrix stiffness-related biomarkers to promote NPC metastasis through the induction of EMT and angiogenesis. Overall, the in-depth exploration of matrix stiffness may provide a strategy for clinical treatment intervention and provide promising targets for clinical NPC treatment.