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

Despite great advances in therapy for breast cancer, more than half of patients still face tumor recurrence and drug resistance. Therefore, a better understanding of tumor progression and drug resistance is needed for developing next-generation therapies. Here, we report the role of galactosyltransferase β3GalT5, a key enzyme responsible for the biosynthesis of SSEA3 which is then converted to SSEA4 and Globo-H. We demonstrated that knockdown of β3GalT5 would destruct the complex formation of SSEA3/SSEA4/Globo-H with FAK/CAV1/AKT/RIP and cause the dissociation of RIP from the complex to interact with FADD, thus triggering cancer cell apoptosis and suppressing metastasis. These findings provide a strategy of therapeutics for breast cancer as demonstrated by the combination use of antibodies against Globo-H and SSEA4.