Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
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- Farhana Yesmin
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Robiul H. Bhuiyan
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Yuhsuke Ohmi
- Department of Medical Technology, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Satoko Yamamoto
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Kei Kaneko
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Yuki Ohkawa
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Pu Zhang
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Kazunori Hamamura
- Department of Pharmacology, Aichi Gakuin University School of Dentistry, Nagoya 464-8650, Japan
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- Nai-Kong V. Cheung
- Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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- Norihiro Kotani
- Department of Biochemistry, Saitama Medical University, Saitama 350-0495, Japan
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- Koichi Honke
- Department of Biochemistry, Kochi University School of Medicine, Nangoku 783-8505, Japan
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- Tetsuya Okajima
- Department of Molecular Biochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-0065, Japan
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- Mariko Kambe
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Orie Tajima
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Keiko Furukawa
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
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- Koichi Furukawa
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
書誌事項
- 公開日
- 2021-12-31
- 資源種別
- journal article
- 権利情報
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- https://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.3390/ijms23010423
- 公開者
- MDPI AG
説明
<jats:p>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.</jats:p>
収録刊行物
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- International Journal of Molecular Sciences
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International Journal of Molecular Sciences 23 (1), 423-, 2021-12-31
MDPI AG
- Tweet
キーワード
- Integrins
- Integrin beta1
- ganglioside; cancer-associated antigen; integrin; GEM/rafts; melanoma
- Antibodies, Monoclonal
- Article
- Collagen Type I
- Mass Spectrometry
- Mice
- Membrane Microdomains
- Phenotype
- Cell Line, Tumor
- Gangliosides
- Cell Adhesion
- Animals
- Humans
- Phosphotyrosine
- Melanoma
- Cell Proliferation
- Signal Transduction
詳細情報 詳細情報について
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- CRID
- 1360576118705248256
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- ISSN
- 14220067
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- PubMed
- 35008849
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
