ST3GAL5-catalysed gangliosides inhibit TGF-β-induced epithelial-mesenchymal transition via TβRI degradation

ABSTRACT: Epithelial-mesenchymal transition (EMT) is pivotal in the initiation and development of cancer cell metastasis. We observed that the abundance of glycosphingolipids (GSLs), especially ganglioside subtypes, decreased significantly during TGF-β-induced EMT in NMuMG mouse mammary epithelial cells and A549 human lung adenocarcinoma cells. Transcriptional profiling showed that TGF-β/SMAD response genes and EMT signatures were strongly enriched in NMuMG cells, along with depletion of UDP-glucose ceramide glucosyltransferase (UGCG), the enzyme that catalyzes the initial step in GSL biosynthesis. Consistent with this finding, genetic or pharmacological inhibition of UGCG promoted TGF-β signaling and TGF-β-induced EMT. UGCG inhibition promoted A549 cell migration, extravasation in the zebrafish xen

SUBMITTER: Prof. Peter ten Dijke 

PROVIDER: S-SCDT-10_15252-EMBJ_2021110553 | biostudies-other |

REPOSITORIES: biostudies-other