Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation
Integrin β1 plays an essential role in the crosstalk between tumor cells and their microenvironment. Aberrant N-glycosylation of integrin β1 was documented to alter integrin β1 expression, dimerization, and biological function. However, the biological function of site-specific N-glycosylation of int...
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doaj-df7917aeee3f4f938175ed9eabc4d3fa2021-02-11T00:06:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01221770177010.3390/ijms22041770Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK ActivationLin Cao0Yurong Wu1Xiuxiu Wang2Xiang Li3Zengqi Tan4Feng Guan5Joint International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi’an 710069, ChinaJoint International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi’an 710069, ChinaJoint International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi’an 710069, ChinaJoint International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi’an 710069, ChinaJoint International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi’an 710069, ChinaJoint International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi’an 710069, ChinaIntegrin β1 plays an essential role in the crosstalk between tumor cells and their microenvironment. Aberrant N-glycosylation of integrin β1 was documented to alter integrin β1 expression, dimerization, and biological function. However, the biological function of site-specific N-glycosylation of integrin β1 on extracellular vesicles is not fully understood. In this study, we mutated putative N-glycosylation sites in different domains of integrin β1. Removal of the N-glycosylation sites on the I-like domain of integrin β1 (termed the Δ4–6 β1 mutant) suppressed focal adhesion kinase (FAK) signaling, cell migration, and adhesion compared with other β1 mutants. Cell adhesion, migration, and activation of FAK were suppressed in recipient MCF7 cells co-cultured with Δ4–6 mutant cells and treated with small extracellular vesicles (sEVs) from Δ4–6 mutant cells. Notably, the wild-type and β1 mutant were both present in sEVs, and could be transferred to recipient cells via sEVs, resulting in changes of cell behavior. Our findings demonstrate the important roles of N-glycosylation of the I-like domain of integrin β1. Moreover, the vesicular Δ4–6 β1 mutant can regulate integrin-mediated functions in recipient cells via sEVs.https://www.mdpi.com/1422-0067/22/4/1770integrin β1N-glycosylationsEVsFAKmigrationadhesion |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lin Cao Yurong Wu Xiuxiu Wang Xiang Li Zengqi Tan Feng Guan |
spellingShingle |
Lin Cao Yurong Wu Xiuxiu Wang Xiang Li Zengqi Tan Feng Guan Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation International Journal of Molecular Sciences integrin β1 N-glycosylation sEVs FAK migration adhesion |
author_facet |
Lin Cao Yurong Wu Xiuxiu Wang Xiang Li Zengqi Tan Feng Guan |
author_sort |
Lin Cao |
title |
Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation |
title_short |
Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation |
title_full |
Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation |
title_fullStr |
Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation |
title_full_unstemmed |
Role of Site-Specific Glycosylation in the I-Like Domain of Integrin β1 in Small Extracellular Vesicle-Mediated Malignant Behavior and FAK Activation |
title_sort |
role of site-specific glycosylation in the i-like domain of integrin β1 in small extracellular vesicle-mediated malignant behavior and fak activation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-02-01 |
description |
Integrin β1 plays an essential role in the crosstalk between tumor cells and their microenvironment. Aberrant N-glycosylation of integrin β1 was documented to alter integrin β1 expression, dimerization, and biological function. However, the biological function of site-specific N-glycosylation of integrin β1 on extracellular vesicles is not fully understood. In this study, we mutated putative N-glycosylation sites in different domains of integrin β1. Removal of the N-glycosylation sites on the I-like domain of integrin β1 (termed the Δ4–6 β1 mutant) suppressed focal adhesion kinase (FAK) signaling, cell migration, and adhesion compared with other β1 mutants. Cell adhesion, migration, and activation of FAK were suppressed in recipient MCF7 cells co-cultured with Δ4–6 mutant cells and treated with small extracellular vesicles (sEVs) from Δ4–6 mutant cells. Notably, the wild-type and β1 mutant were both present in sEVs, and could be transferred to recipient cells via sEVs, resulting in changes of cell behavior. Our findings demonstrate the important roles of N-glycosylation of the I-like domain of integrin β1. Moreover, the vesicular Δ4–6 β1 mutant can regulate integrin-mediated functions in recipient cells via sEVs. |
topic |
integrin β1 N-glycosylation sEVs FAK migration adhesion |
url |
https://www.mdpi.com/1422-0067/22/4/1770 |
work_keys_str_mv |
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