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Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins

Gangliosides have been considered to modulate cell signals in the microdomain of the cell membrane, lipid/rafts, or glycolipid-enriched microdomain/rafts (GEM/rafts). In particular, cancer-associated gangliosides were reported to enhance the malignant properties of cancer cells. In fact, GD2-positiv...

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Autores principales: Yesmin, Farhana, Bhuiyan, Robiul H., Ohmi, Yuhsuke, Yamamoto, Satoko, Kaneko, Kei, Ohkawa, Yuki, Zhang, Pu, Hamamura, Kazunori, Cheung, Nai-Kong V., Kotani, Norihiro, Honke, Koichi, Okajima, Tetsuya, Kambe, Mariko, Tajima, Orie, Furukawa, Keiko, Furukawa, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745508/
https://www.ncbi.nlm.nih.gov/pubmed/35008849
http://dx.doi.org/10.3390/ijms23010423
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author Yesmin, Farhana
Bhuiyan, Robiul H.
Ohmi, Yuhsuke
Yamamoto, Satoko
Kaneko, Kei
Ohkawa, Yuki
Zhang, Pu
Hamamura, Kazunori
Cheung, Nai-Kong V.
Kotani, Norihiro
Honke, Koichi
Okajima, Tetsuya
Kambe, Mariko
Tajima, Orie
Furukawa, Keiko
Furukawa, Koichi
author_facet Yesmin, Farhana
Bhuiyan, Robiul H.
Ohmi, Yuhsuke
Yamamoto, Satoko
Kaneko, Kei
Ohkawa, Yuki
Zhang, Pu
Hamamura, Kazunori
Cheung, Nai-Kong V.
Kotani, Norihiro
Honke, Koichi
Okajima, Tetsuya
Kambe, Mariko
Tajima, Orie
Furukawa, Keiko
Furukawa, Koichi
author_sort Yesmin, Farhana
collection PubMed
description Gangliosides have been considered to modulate cell signals in the microdomain of the cell membrane, lipid/rafts, or glycolipid-enriched microdomain/rafts (GEM/rafts). In particular, cancer-associated gangliosides were reported to enhance the malignant properties of cancer cells. In fact, GD2-positive (GD2+) cells showed increased proliferation, invasion, and adhesion, compared with GD2-negative (GD2−) cells. However, the precise mechanisms by which gangliosides regulate cell signaling in GEM/rafts are not well understood. In order to analyze the roles of ganglioside GD2 in the malignant properties of melanoma cells, we searched for GD2-associating molecules on the cell membrane using the enzyme-mediated activation of radical sources combined with mass spectrometry, and integrin β1 was identified as a representative GD2-associating molecule. Then, we showed the physical association of GD2 and integrin β1 by immunoprecipitation/immunoblotting. Close localization was also shown by immuno-cytostaining and the proximity ligation assay. During cell adhesion, GD2+ cells showed multiple phospho-tyrosine bands, i.e., the epithelial growth factor receptor and focal adhesion kinase. The knockdown of integrin β1 revealed that the increased malignant phenotypes in GD2+ cells were clearly cancelled. Furthermore, the phosphor-tyrosine bands detected during the adhesion of GD2+ cells almost completely disappeared after the knockdown of integrin β1. Finally, immunoblotting to examine the intracellular distribution of integrins during cell adhesion revealed that large amounts of integrin β1 were localized in GEM/raft fractions in GD2+ cells before and just after cell adhesion, with the majority being localized in the non-raft fractions in GD2− cells. All these results suggest that GD2 and integrin β1 cooperate in GEM/rafts, leading to enhanced malignant phenotypes of melanomas.
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spelling pubmed-87455082022-01-11 Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins Yesmin, Farhana Bhuiyan, Robiul H. Ohmi, Yuhsuke Yamamoto, Satoko Kaneko, Kei Ohkawa, Yuki Zhang, Pu Hamamura, Kazunori Cheung, Nai-Kong V. Kotani, Norihiro Honke, Koichi Okajima, Tetsuya Kambe, Mariko Tajima, Orie Furukawa, Keiko Furukawa, Koichi Int J Mol Sci Article Gangliosides have been considered to modulate cell signals in the microdomain of the cell membrane, lipid/rafts, or glycolipid-enriched microdomain/rafts (GEM/rafts). In particular, cancer-associated gangliosides were reported to enhance the malignant properties of cancer cells. In fact, GD2-positive (GD2+) cells showed increased proliferation, invasion, and adhesion, compared with GD2-negative (GD2−) cells. However, the precise mechanisms by which gangliosides regulate cell signaling in GEM/rafts are not well understood. In order to analyze the roles of ganglioside GD2 in the malignant properties of melanoma cells, we searched for GD2-associating molecules on the cell membrane using the enzyme-mediated activation of radical sources combined with mass spectrometry, and integrin β1 was identified as a representative GD2-associating molecule. Then, we showed the physical association of GD2 and integrin β1 by immunoprecipitation/immunoblotting. Close localization was also shown by immuno-cytostaining and the proximity ligation assay. During cell adhesion, GD2+ cells showed multiple phospho-tyrosine bands, i.e., the epithelial growth factor receptor and focal adhesion kinase. The knockdown of integrin β1 revealed that the increased malignant phenotypes in GD2+ cells were clearly cancelled. Furthermore, the phosphor-tyrosine bands detected during the adhesion of GD2+ cells almost completely disappeared after the knockdown of integrin β1. Finally, immunoblotting to examine the intracellular distribution of integrins during cell adhesion revealed that large amounts of integrin β1 were localized in GEM/raft fractions in GD2+ cells before and just after cell adhesion, with the majority being localized in the non-raft fractions in GD2− cells. All these results suggest that GD2 and integrin β1 cooperate in GEM/rafts, leading to enhanced malignant phenotypes of melanomas. MDPI 2021-12-31 /pmc/articles/PMC8745508/ /pubmed/35008849 http://dx.doi.org/10.3390/ijms23010423 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yesmin, Farhana
Bhuiyan, Robiul H.
Ohmi, Yuhsuke
Yamamoto, Satoko
Kaneko, Kei
Ohkawa, Yuki
Zhang, Pu
Hamamura, Kazunori
Cheung, Nai-Kong V.
Kotani, Norihiro
Honke, Koichi
Okajima, Tetsuya
Kambe, Mariko
Tajima, Orie
Furukawa, Keiko
Furukawa, Koichi
Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
title Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
title_full Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
title_fullStr Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
title_full_unstemmed Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
title_short Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
title_sort ganglioside gd2 enhances the malignant phenotypes of melanoma cells by cooperating with integrins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745508/
https://www.ncbi.nlm.nih.gov/pubmed/35008849
http://dx.doi.org/10.3390/ijms23010423
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