Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells

Abstract

Abstract:In the last decade, particular sphingolipids have become renowned for their participation in cell membrane functions and signaling proceedings that regulate a wide array of cellular manners. Ceramide is a major molecule of sphingolipids metabolism. It plays vital roles in mediating the major cellular functions such as cell differentiation, cell-to-cell communication, apoptosis, and proliferation. Recent studies have shown that ceramide metabolism and their metabolic enzymes take important role during migration and cell mobility process. However, the molecular mechanism of sphingolipids involved is unknown. Our efforts in this study, which are serving mechanistically the understanding of ceramide, will be shade some light on this unknown. In this work, particularly, we looked at the effect of ceramide syntheses on migration ability of UM-SCC-22A head and neck squamous carcinoma cells. Briefly, we identified that alterations in ceramide metabolism by pharmacological inhibitor fumonisin B1, reducing bioactive ceramides, results in activation of the TGF-ß receptor type I and II (TßRI/II) cell surface localization and, leading to increased cell migration/invasion in UM-SCC-22A head and neck squamous carcinoma cells. On the other hand, primary cilia length in UM-SCC-22A cells did not changed by decreased ceramide amount. Thus, these data reveal that ceramide synthases/ceramide is a novel factor that regulates TßRI/II to the primary cilium, controlling cell migration and cancer metastasis.