Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/α 5β1 integrin/epidermal growth factor receptor interactions

Xiao Qi Wang; Ping Sun; Amy S. Paller

doi:10.1111/j.0022-202X.2005.23669.x

Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/α ₅β₁ integrin/epidermal growth factor receptor interactions

Xiao Qi Wang^*, Ping Sun, Amy S. Paller

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting α₅β₁ integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAcα2 → 3Galβ1 → 3GalNAcβ1 → 4(NeuAcα2 → 8NeuAcα2 → 3)Galβ1 → 4Glcβ1-Cer (GT1b) or NeuAcα2 → 3Galβ1 - 4Glcβ1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with α₅β₁ integrin or uPAR/α₅β ₁ integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin α₅β ₁.

Original language	English (US)
Pages (from-to)	839-848
Number of pages	10
Journal	Journal of Investigative Dermatology
Volume	124
Issue number	4
DOIs	https://doi.org/10.1111/j.0022-202X.2005.23669.x
State	Published - Apr 2005

Funding

This work was supported by the National Institutes of Health Grant R01 AR44619, the Fujisawa Healthcare, Inc. Research Endowment (ASP), and the Dermatology Foundation (XQW).

Keywords

Antisense
FAK
GPI
PPPP
Sialidase

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Dermatology
Cell Biology

Access to Document

10.1111/j.0022-202X.2005.23669.x

Cite this

@article{d8092dcea25f4e8e8471a80a506de8cd,

title = "Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/α 5β1 integrin/epidermal growth factor receptor interactions",

abstract = "The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting α5β1 integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAcα2 → 3Galβ1 → 3GalNAcβ1 → 4(NeuAcα2 → 8NeuAcα2 → 3)Galβ1 → 4Glcβ1-Cer (GT1b) or NeuAcα2 → 3Galβ1 - 4Glcβ1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with α5β1 integrin or uPAR/α5β 1 integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin α5β 1.",

keywords = "Antisense, FAK, GPI, PPPP, Sialidase",

author = "Wang, {Xiao Qi} and Ping Sun and Paller, {Amy S.}",

note = "Funding Information: This work was supported by the National Institutes of Health Grant R01 AR44619, the Fujisawa Healthcare, Inc. Research Endowment (ASP), and the Dermatology Foundation (XQW).",

year = "2005",

month = apr,

doi = "10.1111/j.0022-202X.2005.23669.x",

language = "English (US)",

volume = "124",

pages = "839--848",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Nature Publishing Group",

number = "4",

}

Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/α ₅β₁ integrin/epidermal growth factor receptor interactions. / Wang, Xiao Qi; Sun, Ping; Paller, Amy S.
In: Journal of Investigative Dermatology, Vol. 124, No. 4, 04.2005, p. 839-848.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/α 5β1 integrin/epidermal growth factor receptor interactions

AU - Wang, Xiao Qi

AU - Sun, Ping

AU - Paller, Amy S.

N1 - Funding Information: This work was supported by the National Institutes of Health Grant R01 AR44619, the Fujisawa Healthcare, Inc. Research Endowment (ASP), and the Dermatology Foundation (XQW).

PY - 2005/4

Y1 - 2005/4

N2 - The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting α5β1 integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAcα2 → 3Galβ1 → 3GalNAcβ1 → 4(NeuAcα2 → 8NeuAcα2 → 3)Galβ1 → 4Glcβ1-Cer (GT1b) or NeuAcα2 → 3Galβ1 - 4Glcβ1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with α5β1 integrin or uPAR/α5β 1 integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin α5β 1.

AB - The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting α5β1 integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAcα2 → 3Galβ1 → 3GalNAcβ1 → 4(NeuAcα2 → 8NeuAcα2 → 3)Galβ1 → 4Glcβ1-Cer (GT1b) or NeuAcα2 → 3Galβ1 - 4Glcβ1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with α5β1 integrin or uPAR/α5β 1 integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin α5β 1.

KW - Antisense

KW - FAK

KW - GPI

KW - PPPP

KW - Sialidase

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DO - 10.1111/j.0022-202X.2005.23669.x

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SN - 0022-202X

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SP - 839

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JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

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