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© 2021 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
Author
Yesmin, Farhana 1 ; Bhuiyan, Robiul H 2   VIAFID ORCID Logo  ; Ohmi, Yuhsuke 3 ; Yamamoto, Satoko 2 ; Kaneko, Kei 2 ; Ohkawa, Yuki 4 ; Zhang, Pu 1 ; Hamamura, Kazunori 5   VIAFID ORCID Logo  ; Cheung, Nai-Kong V 6   VIAFID ORCID Logo  ; Kotani, Norihiro 7 ; Honke, Koichi 8   VIAFID ORCID Logo  ; Okajima, Tetsuya 9   VIAFID ORCID Logo  ; Kambe, Mariko 2 ; Tajima, Orie 2 ; Furukawa, Keiko 2 ; Furukawa, Koichi 1   VIAFID ORCID Logo 

 Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan; [email protected] (F.Y.); [email protected] (R.H.B.); [email protected] (S.Y.); [email protected] (K.K.); [email protected] (Y.O.); [email protected] (P.Z.); [email protected] (M.K.); [email protected] (O.T.); [email protected] (K.F.); Department of Molecular Biochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-0065, Japan; [email protected] 
 Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan; [email protected] (F.Y.); [email protected] (R.H.B.); [email protected] (S.Y.); [email protected] (K.K.); [email protected] (Y.O.); [email protected] (P.Z.); [email protected] (M.K.); [email protected] (O.T.); [email protected] (K.F.) 
 Department of Medical Technology, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan; [email protected] 
 Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan; [email protected] (F.Y.); [email protected] (R.H.B.); [email protected] (S.Y.); [email protected] (K.K.); [email protected] (Y.O.); [email protected] (P.Z.); [email protected] (M.K.); [email protected] (O.T.); [email protected] (K.F.); Department of Glyco-Oncology and Medical Biochemistry, Osaka International Cancer Institute, Osaka 541-8567, Japan 
 Department of Pharmacology, Aichi Gakuin University School of Dentistry, Nagoya 464-8650, Japan; [email protected] 
 Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; [email protected] 
 Department of Biochemistry, Saitama Medical University, Saitama 350-0495, Japan; [email protected] 
 Department of Biochemistry, Kochi University School of Medicine, Nangoku 783-8505, Japan; [email protected] 
 Department of Molecular Biochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-0065, Japan; [email protected] 
First page
423
Publication year
2022
Publication date
2022
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2618239585
Copyright
© 2021 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.