Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer

The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, an Globo-H specifically expressed on cancer cells are found to correlat with tumor progression and metastasis, but the functional role of these GSLs and the key enzyme β1,3-galactosyltransferase (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Her we show that the expression of β3GalT5 significantly correlates wit tumor progression and poor survival in patients, and the globo series GSLs in breast cancer cells form a complex in membrane lipi raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) whic then interact with AKT and receptor-interacting protein kinase (RIP) respectively. Knockdown of β3GalT5 disrupts the complex and in duces apoptosis through dissociation of RIP from the complex t interact with the Fas death domain (FADD) and trigger the Fas dependent pathway. This finding provides a link between SSEA3 SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor pro gression and apoptosis and suggests a direction for the treatment o breast cancer, as demonstrated by the combined use of antibodie against Globo-H and SSEA4.