Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells
Abstract GalNAc-disialyl Lc4 (GalNAc-DSLc4) was reported as a novel antigen that associated with malignant features of renal cell cancers (RCCs). To clarify roles of GalNAc-DSLc4 in malignant properties of RCCs, we identified B4GalNAc-T2 as a responsible gene for the synthesis of GalNAc-DSLc4, and p...
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2018
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oai:doaj.org-article:6931623c8cee4e688a3f16eaa3d0c7412021-12-02T15:08:14ZRoles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells10.1038/s41598-018-25521-62045-2322https://doaj.org/article/6931623c8cee4e688a3f16eaa3d0c7412018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25521-6https://doaj.org/toc/2045-2322Abstract GalNAc-disialyl Lc4 (GalNAc-DSLc4) was reported as a novel antigen that associated with malignant features of renal cell cancers (RCCs). To clarify roles of GalNAc-DSLc4 in malignant properties of RCCs, we identified B4GalNAc-T2 as a responsible gene for the synthesis of GalNAc-DSLc4, and prepared stable transfectants of GalNAc-T2 cDNA using VMRC-RCW cells, resulting in the establishment of high expressants of GalNAc-DSLc4. They showed increased proliferation and invasion, and specific adhesion to laminin. In the transfectants, PI3K/Akt signals were highly activated by serum stimulation or adhesion to laminin. GalNAc-DSLc4 was co-localized in lipid rafts with integrin β1 and caveolin-1 in both immunoblotting of fractionated detergent extracts and immunocytostaining, particularly when stimulated with serum. Masking of GalNAc-DSLc4 with antibodies as well as PI3K inhibitor suppressed malignant properties of the transfectants. These results suggested that GalNAc-DSLc4 is involved in malignant properties of RCCs by forming a molecular complex with integrins in lipid rafts.Akiko TsuchidaMotohiro SendaAkihiro ItoSeiichi SaitoMakoto KisoTakayuki AndoAnne Harduin-LepersAkio MatsudaKeiko FurukawaKoichi FurukawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) |
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Medicine R Science Q Akiko Tsuchida Motohiro Senda Akihiro Ito Seiichi Saito Makoto Kiso Takayuki Ando Anne Harduin-Lepers Akio Matsuda Keiko Furukawa Koichi Furukawa Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells |
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Abstract GalNAc-disialyl Lc4 (GalNAc-DSLc4) was reported as a novel antigen that associated with malignant features of renal cell cancers (RCCs). To clarify roles of GalNAc-DSLc4 in malignant properties of RCCs, we identified B4GalNAc-T2 as a responsible gene for the synthesis of GalNAc-DSLc4, and prepared stable transfectants of GalNAc-T2 cDNA using VMRC-RCW cells, resulting in the establishment of high expressants of GalNAc-DSLc4. They showed increased proliferation and invasion, and specific adhesion to laminin. In the transfectants, PI3K/Akt signals were highly activated by serum stimulation or adhesion to laminin. GalNAc-DSLc4 was co-localized in lipid rafts with integrin β1 and caveolin-1 in both immunoblotting of fractionated detergent extracts and immunocytostaining, particularly when stimulated with serum. Masking of GalNAc-DSLc4 with antibodies as well as PI3K inhibitor suppressed malignant properties of the transfectants. These results suggested that GalNAc-DSLc4 is involved in malignant properties of RCCs by forming a molecular complex with integrins in lipid rafts. |
format |
article |
author |
Akiko Tsuchida Motohiro Senda Akihiro Ito Seiichi Saito Makoto Kiso Takayuki Ando Anne Harduin-Lepers Akio Matsuda Keiko Furukawa Koichi Furukawa |
author_facet |
Akiko Tsuchida Motohiro Senda Akihiro Ito Seiichi Saito Makoto Kiso Takayuki Ando Anne Harduin-Lepers Akio Matsuda Keiko Furukawa Koichi Furukawa |
author_sort |
Akiko Tsuchida |
title |
Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells |
title_short |
Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells |
title_full |
Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells |
title_fullStr |
Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells |
title_full_unstemmed |
Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells |
title_sort |
roles of galnac-disialyl lactotetraosyl antigens in renal cancer cells |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/6931623c8cee4e688a3f16eaa3d0c741 |
work_keys_str_mv |
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