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The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9

Research output: Contribution to journalArticle

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The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9. / Beatson, Richard; Tajadura-Ortega, Virginia; Achkova, Daniela Yordanova; Picco, Gianfranco; Tsourouktsoglou, Theodora-Dorita ; Klausing, Sandra; Hillier, Matthew; Maher, John; Noll, Thomas; Crocker, Paul; Taylor-Papadimitriou, Joyce; Burchell, Joy Marilyn.

In: Nature Immunology, Vol. 17, 05.09.2016, p. 1273-1281.

Research output: Contribution to journalArticle

Harvard

Beatson, R, Tajadura-Ortega, V, Achkova, DY, Picco, G, Tsourouktsoglou, T-D, Klausing, S, Hillier, M, Maher, J, Noll, T, Crocker, P, Taylor-Papadimitriou, J & Burchell, JM 2016, 'The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9', Nature Immunology, vol. 17, pp. 1273-1281. https://doi.org/10.1038/ni.3552

APA

Beatson, R., Tajadura-Ortega, V., Achkova, D. Y., Picco, G., Tsourouktsoglou, T-D., Klausing, S., Hillier, M., Maher, J., Noll, T., Crocker, P., Taylor-Papadimitriou, J., & Burchell, J. M. (2016). The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9. Nature Immunology, 17, 1273-1281. https://doi.org/10.1038/ni.3552

Vancouver

Beatson R, Tajadura-Ortega V, Achkova DY, Picco G, Tsourouktsoglou T-D, Klausing S et al. The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9. Nature Immunology. 2016 Sep 5;17:1273-1281. https://doi.org/10.1038/ni.3552

Author

Beatson, Richard ; Tajadura-Ortega, Virginia ; Achkova, Daniela Yordanova ; Picco, Gianfranco ; Tsourouktsoglou, Theodora-Dorita ; Klausing, Sandra ; Hillier, Matthew ; Maher, John ; Noll, Thomas ; Crocker, Paul ; Taylor-Papadimitriou, Joyce ; Burchell, Joy Marilyn. / The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9. In: Nature Immunology. 2016 ; Vol. 17. pp. 1273-1281.

Bibtex Download

@article{2a4d9b3bd09f4e2194866262d5a8fcb5,
title = "The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9",
abstract = "Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9.",
author = "Richard Beatson and Virginia Tajadura-Ortega and Achkova, {Daniela Yordanova} and Gianfranco Picco and Theodora-Dorita Tsourouktsoglou and Sandra Klausing and Matthew Hillier and John Maher and Thomas Noll and Paul Crocker and Joyce Taylor-Papadimitriou and Burchell, {Joy Marilyn}",
year = "2016",
month = sep,
day = "5",
doi = "10.1038/ni.3552",
language = "English",
volume = "17",
pages = "1273--1281",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - The mucin MUC1 modulates the tumor immune microenvironment through the engagement of Siglec-9

AU - Beatson, Richard

AU - Tajadura-Ortega, Virginia

AU - Achkova, Daniela Yordanova

AU - Picco, Gianfranco

AU - Tsourouktsoglou, Theodora-Dorita

AU - Klausing, Sandra

AU - Hillier, Matthew

AU - Maher, John

AU - Noll, Thomas

AU - Crocker, Paul

AU - Taylor-Papadimitriou, Joyce

AU - Burchell, Joy Marilyn

PY - 2016/9/5

Y1 - 2016/9/5

N2 - Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9.

AB - Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9.

U2 - 10.1038/ni.3552

DO - 10.1038/ni.3552

M3 - Article

VL - 17

SP - 1273

EP - 1281

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

ER -

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