期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 9, 页码 3518-3523出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1816946116
关键词
beta 3GalT5; SSEA3; SSEA4; Globo-H; FAK
资金
- Summit Program of the Genomics Research Center, Academia Sinica, Taiwan
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 beta 1,3-galactosyltransferase V (beta 3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Here we show that the expression of beta 3GalT5 significantly correlates with tumor progression and poor survival in patients, and the globoseries 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 beta 3GalT5 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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