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Title :Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells
Authors :Tsuchida, Akio
Senda, Motohiro
Ito, Akihiro
Saito, Seiichi
Kiso, Makoto
Ando, Takayuki
Harduin-Lepers, Anne
Matsuda, Akio
Furukawa, Keiko
Furukawa, Koichi
Issue Date :4-May-2018
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.
URL :https://doi.org/10.1038/s41598-018-25521-6
Type Local :雑誌掲載論文
ISSN :2045-2322
Publisher :Springer Nature
URI :http://hdl.handle.net/20.500.12000/47490
Citation :Scientific Reports Vol.8
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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