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Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer

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Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer. / Legler, Karen; Rosprim, Ricarda; Karius, Tosca; Eylmann, Kathrin; Rossberg, Maila; Wirtz, Ralph M; Müller, Volkmar; Witzel, Isabell; Schmalfeldt, Barbara; Milde-Langosch, Karin; Oliveira-Ferrer, Leticia.

In: BRIT J CANCER, Vol. 118, No. 6, 20.03.2018, p. 847-856.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Legler, K, Rosprim, R, Karius, T, Eylmann, K, Rossberg, M, Wirtz, RM, Müller, V, Witzel, I, Schmalfeldt, B, Milde-Langosch, K & Oliveira-Ferrer, L 2018, 'Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer', BRIT J CANCER, vol. 118, no. 6, pp. 847-856. https://doi.org/10.1038/bjc.2017.472

APA

Legler, K., Rosprim, R., Karius, T., Eylmann, K., Rossberg, M., Wirtz, R. M., Müller, V., Witzel, I., Schmalfeldt, B., Milde-Langosch, K., & Oliveira-Ferrer, L. (2018). Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer. BRIT J CANCER, 118(6), 847-856. https://doi.org/10.1038/bjc.2017.472

Vancouver

Legler K, Rosprim R, Karius T, Eylmann K, Rossberg M, Wirtz RM et al. Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer. BRIT J CANCER. 2018 Mar 20;118(6):847-856. https://doi.org/10.1038/bjc.2017.472

Bibtex

@article{13f5ffa7347c4ad59d3e71672b379fd8,
title = "Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer",
abstract = "BACKGROUND: Alterations in protein glycosylation have been related to malignant transformation and tumour progression. We recently showed that low mRNA levels of Golgi alpha-mannosidase MAN1A1 correlate with poor prognosis in breast cancer patients.METHODS: We analysed the role of MAN1A1 on a protein level using western blot analysis (n=105) and studied the impact of MAN1A1-related glycosylation on the prognostic relevance of adhesion molecules involved in breast cancer using microarray data (n=194). Functional consequences of mannosidase inhibition using the inhibitor kifunensine or MAN1A1 silencing were investigated in breast cancer cells in vitro.RESULTS: Patients with low/moderate MAN1A1 expression in tumours showed significantly shorter disease-free intervals than those with high MAN1A1 levels (P=0.005). Moreover, low MAN1A1 expression correlated significantly with nodal status, grading and brain metastasis. At an mRNA level, membrane proteins ALCAM and CD24 were only significantly prognostic in tumours with high MAN1A1 expression. In vitro, reduced MAN1A1 expression or mannosidase inhibition led to a significantly increased adhesion of breast cancer cells to endothelial cells.CONCLUSIONS: Our study demonstrates the prognostic role of MAN1A1 in breast cancer by affecting the adhesive properties of tumour cells and the strong influence of this glycosylation enzyme on the prognostic impact of some adhesion proteins.",
keywords = "Journal Article",
author = "Karen Legler and Ricarda Rosprim and Tosca Karius and Kathrin Eylmann and Maila Rossberg and Wirtz, {Ralph M} and Volkmar M{\"u}ller and Isabell Witzel and Barbara Schmalfeldt and Karin Milde-Langosch and Leticia Oliveira-Ferrer",
year = "2018",
month = mar,
day = "20",
doi = "10.1038/bjc.2017.472",
language = "English",
volume = "118",
pages = "847--856",
journal = "BRIT J CANCER",
issn = "0007-0920",
publisher = "NATURE PUBLISHING GROUP",
number = "6",

}

RIS

TY - JOUR

T1 - Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer

AU - Legler, Karen

AU - Rosprim, Ricarda

AU - Karius, Tosca

AU - Eylmann, Kathrin

AU - Rossberg, Maila

AU - Wirtz, Ralph M

AU - Müller, Volkmar

AU - Witzel, Isabell

AU - Schmalfeldt, Barbara

AU - Milde-Langosch, Karin

AU - Oliveira-Ferrer, Leticia

PY - 2018/3/20

Y1 - 2018/3/20

N2 - BACKGROUND: Alterations in protein glycosylation have been related to malignant transformation and tumour progression. We recently showed that low mRNA levels of Golgi alpha-mannosidase MAN1A1 correlate with poor prognosis in breast cancer patients.METHODS: We analysed the role of MAN1A1 on a protein level using western blot analysis (n=105) and studied the impact of MAN1A1-related glycosylation on the prognostic relevance of adhesion molecules involved in breast cancer using microarray data (n=194). Functional consequences of mannosidase inhibition using the inhibitor kifunensine or MAN1A1 silencing were investigated in breast cancer cells in vitro.RESULTS: Patients with low/moderate MAN1A1 expression in tumours showed significantly shorter disease-free intervals than those with high MAN1A1 levels (P=0.005). Moreover, low MAN1A1 expression correlated significantly with nodal status, grading and brain metastasis. At an mRNA level, membrane proteins ALCAM and CD24 were only significantly prognostic in tumours with high MAN1A1 expression. In vitro, reduced MAN1A1 expression or mannosidase inhibition led to a significantly increased adhesion of breast cancer cells to endothelial cells.CONCLUSIONS: Our study demonstrates the prognostic role of MAN1A1 in breast cancer by affecting the adhesive properties of tumour cells and the strong influence of this glycosylation enzyme on the prognostic impact of some adhesion proteins.

AB - BACKGROUND: Alterations in protein glycosylation have been related to malignant transformation and tumour progression. We recently showed that low mRNA levels of Golgi alpha-mannosidase MAN1A1 correlate with poor prognosis in breast cancer patients.METHODS: We analysed the role of MAN1A1 on a protein level using western blot analysis (n=105) and studied the impact of MAN1A1-related glycosylation on the prognostic relevance of adhesion molecules involved in breast cancer using microarray data (n=194). Functional consequences of mannosidase inhibition using the inhibitor kifunensine or MAN1A1 silencing were investigated in breast cancer cells in vitro.RESULTS: Patients with low/moderate MAN1A1 expression in tumours showed significantly shorter disease-free intervals than those with high MAN1A1 levels (P=0.005). Moreover, low MAN1A1 expression correlated significantly with nodal status, grading and brain metastasis. At an mRNA level, membrane proteins ALCAM and CD24 were only significantly prognostic in tumours with high MAN1A1 expression. In vitro, reduced MAN1A1 expression or mannosidase inhibition led to a significantly increased adhesion of breast cancer cells to endothelial cells.CONCLUSIONS: Our study demonstrates the prognostic role of MAN1A1 in breast cancer by affecting the adhesive properties of tumour cells and the strong influence of this glycosylation enzyme on the prognostic impact of some adhesion proteins.

KW - Journal Article

U2 - 10.1038/bjc.2017.472

DO - 10.1038/bjc.2017.472

M3 - SCORING: Journal article

C2 - 29381688

VL - 118

SP - 847

EP - 856

JO - BRIT J CANCER

JF - BRIT J CANCER

SN - 0007-0920

IS - 6

ER -