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

Proceedings of the National Academy of Sciences of the United States of America
Po-Kai ChuangChi-Huey Wong

Abstract

The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, and Globo-H specifically expressed on cancer cells are found to correlate with tumor progression and metastasis, but the functional roles of these GSLs and the key enzyme β1,3-galactosyltransferase V (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Here we show that the expression of β3GalT5 significantly correlates with tumor progression and poor survival in patients, and the globo-series GSLs in breast cancer cells form a complex in membrane lipid raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) which then interact with AKT and receptor-interacting protein kinase (RIP), respectively. Knockdown of β3GalT5 disrupts the complex and induces apoptosis through dissociation of RIP from the complex to 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 progression and apoptosis and suggests a direction for the treatment of breast cancer, as demonstrated by the combined use of antibodies against Globo-H and SSEA4.

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Citations

Apr 3, 2020·FEBS Open Bio·Shuuji MawaribuchiYuzuru Ito
Jul 28, 2020·Journal of Bioenergetics and Biomembranes·Wojciech SzlasaJulita Kulbacka
Nov 26, 2019·Xenotransplantation·Yoshihide NannoChristopher Burlak
Dec 6, 2019·International Journal of Molecular Sciences·Miroslav MachalaJan Vondráček
Sep 8, 2020·Journal of Cellular and Molecular Medicine·Li-Hsun LinHong-Lin Chan
Mar 17, 2021·Molecular Cancer Therapeutics·Ming-Chen YangMing-Tain Lai
Aug 10, 2021·ACS Chemical Biology·Ruey-Herng LeeChi-Huey Wong

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