Lewis glycosphingolipids as critical determinants of TRAIL sensitivity in cancer cells.

Autor: Fukuoka T; Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Moriwaki K; Department of Biochemistry, Toho University School of Medicine, Ota-ku, Tokyo, 143-8540, Japan. kenta.moriwaki@med.toho-u.ac.jp., Takamatsu S; Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Kondo J; Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.; Department of Clinical Bio-resource Research and Development, Graduate School of Medicine Kyoto University, Sakyouku, Kyoto, 606-8501, Japan., Tanaka-Okamoto M; Department of Molecular Biology, Osaka International Cancer Institute, Chuo-ku, Osaka, 541-8567, Japan., Tomioka A; Molecular and Cellular Glycoproteomics Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, 305-8565, Japan., Semba M; Department of Biochemistry, Toho University School of Medicine, Ota-ku, Tokyo, 143-8540, Japan.; Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Katsushika-Ku, Tokyo, 125-8585, Japan., Komazawa-Sakon S; Department of Biochemistry, Toho University School of Medicine, Ota-ku, Tokyo, 143-8540, Japan., Kamada Y; Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.; Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Kaji H; Molecular and Cellular Glycoproteomics Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, 305-8565, Japan., Miyamoto Y; Department of Molecular Biology, Osaka International Cancer Institute, Chuo-ku, Osaka, 541-8567, Japan., Inoue M; Department of Clinical Bio-resource Research and Development, Graduate School of Medicine Kyoto University, Sakyouku, Kyoto, 606-8501, Japan., Bessho K; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Miyoshi Y; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Ozono K; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Nakano H; Department of Biochemistry, Toho University School of Medicine, Ota-ku, Tokyo, 143-8540, Japan., Miyoshi E; Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. emiyoshi@sahs.med.osaka-u.ac.jp.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2022 Sep; Vol. 41 (38), pp. 4385-4396. Date of Electronic Publication: 2022 Aug 15.
DOI: 10.1038/s41388-022-02434-3
Abstrakt: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cancer cell death and contributes to tumor rejection by cytotoxic lymphocytes in cancer immunosurveillance and immunotherapy. TRAIL and TRAIL receptor agonists have garnered wide popularity as promising agents for cancer therapy. We previously demonstrated that the loss of fucosylation in cancer cells impairs TRAIL sensitivity; however, the precise structures of the fucosylated glycans that regulate TRAIL sensitivity and their carrier molecules remain elusive. Herein, we observed that Lewis glycans among various fucosylated glycans positively regulate TRAIL-induced cell death. Specifically, Lewis glycans on lacto/neolacto glycosphingolipids, but not glycoproteins including TRAIL receptors, enhanced TRAIL-induced formation of the cytosolic caspase 8 complex, without affecting the formation of the membranous receptor complex. Furthermore, type I Lewis glycan expression in colon cancer cell lines and patient-derived cancer organoids was positively correlated with TRAIL sensitivity. These findings provide novel insights into the regulatory mechanism of TRAIL-induced cell death and facilitate the identification of novel predictive biomarkers for TRAIL-related cancer therapies in future.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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