Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation: impact of N-glycosylation on tumour cell aggregation

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Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation: impact of N-glycosylation on tumour cell aggregation. / Hamester, Fabienne; Legler, Karen; Wichert, Beatrice; Kelle, Nicole; Eylmann, Kathrin; Rossberg, Maila; Ding, Yi; Kürti, Sascha; Schmalfeldt, Barbara; Milde-Langosch, Karin; Oliveira-Ferrer, Leticia.

In: BRIT J CANCER, Vol. 121, No. 11, 11.2019, p. 944-953.

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@article{b1b0cea2f06d4620b31db3905c2d1e4f,
title = "Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation: impact of N-glycosylation on tumour cell aggregation",
abstract = "BACKGROUND: Maturation of complex N-glycans involves the action of Golgi mannosidases and plays a major role in cancer progression. We recently showed a favourable prognostic role of α-mannosidase MAN1A1 in breast cancer mainly caused by alteration of certain adhesion molecules.METHODS: We analysed the protein expression of MAN1A1 in ovarian cancer (n = 204) using western blot and studied the impact of MAN1A1 itself and of MAN1A1-related glycosylation on the prognostic relevance of two adhesion molecules. Functional consequences of mannosidase inhibition using kifunensine and MAN1A1 knock out were investigated in ovarian cancer cells in vitro.RESULTS: Patients with high MAN1A1 expression in tumours showed significantly shorter RFS than those with low-MAN1A1 levels. Moreover, high MAN1A1 expression correlated significantly with advanced stage, lymph node involvement and distant metastasis. Further, the glycosylated adhesion molecule ALCAM reveals a significant adverse prognostic effect only in the presence of high MAN1A1 expression. In spheroid-formation assays, mannosidase inhibition and especially MAN1A1 knock out led to strong reduction of tumour cell aggregation.CONCLUSIONS: Our study demonstrates the unfavourable prognostic role of MAN1A1 in ovarian cancer, probably caused by an altered ability of spheroid formation, and the strong influence of this glycosylation enzyme on the prognostic impact of ALCAM.",
author = "Fabienne Hamester and Karen Legler and Beatrice Wichert and Nicole Kelle and Kathrin Eylmann and Maila Rossberg and Yi Ding and Sascha K{\"u}rti and Barbara Schmalfeldt and Karin Milde-Langosch and Leticia Oliveira-Ferrer",
year = "2019",
month = "11",
doi = "10.1038/s41416-019-0607-2",
language = "English",
volume = "121",
pages = "944--953",
journal = "BRIT J CANCER",
issn = "0007-0920",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation: impact of N-glycosylation on tumour cell aggregation

AU - Hamester, Fabienne

AU - Legler, Karen

AU - Wichert, Beatrice

AU - Kelle, Nicole

AU - Eylmann, Kathrin

AU - Rossberg, Maila

AU - Ding, Yi

AU - Kürti, Sascha

AU - Schmalfeldt, Barbara

AU - Milde-Langosch, Karin

AU - Oliveira-Ferrer, Leticia

PY - 2019/11

Y1 - 2019/11

N2 - BACKGROUND: Maturation of complex N-glycans involves the action of Golgi mannosidases and plays a major role in cancer progression. We recently showed a favourable prognostic role of α-mannosidase MAN1A1 in breast cancer mainly caused by alteration of certain adhesion molecules.METHODS: We analysed the protein expression of MAN1A1 in ovarian cancer (n = 204) using western blot and studied the impact of MAN1A1 itself and of MAN1A1-related glycosylation on the prognostic relevance of two adhesion molecules. Functional consequences of mannosidase inhibition using kifunensine and MAN1A1 knock out were investigated in ovarian cancer cells in vitro.RESULTS: Patients with high MAN1A1 expression in tumours showed significantly shorter RFS than those with low-MAN1A1 levels. Moreover, high MAN1A1 expression correlated significantly with advanced stage, lymph node involvement and distant metastasis. Further, the glycosylated adhesion molecule ALCAM reveals a significant adverse prognostic effect only in the presence of high MAN1A1 expression. In spheroid-formation assays, mannosidase inhibition and especially MAN1A1 knock out led to strong reduction of tumour cell aggregation.CONCLUSIONS: Our study demonstrates the unfavourable prognostic role of MAN1A1 in ovarian cancer, probably caused by an altered ability of spheroid formation, and the strong influence of this glycosylation enzyme on the prognostic impact of ALCAM.

AB - BACKGROUND: Maturation of complex N-glycans involves the action of Golgi mannosidases and plays a major role in cancer progression. We recently showed a favourable prognostic role of α-mannosidase MAN1A1 in breast cancer mainly caused by alteration of certain adhesion molecules.METHODS: We analysed the protein expression of MAN1A1 in ovarian cancer (n = 204) using western blot and studied the impact of MAN1A1 itself and of MAN1A1-related glycosylation on the prognostic relevance of two adhesion molecules. Functional consequences of mannosidase inhibition using kifunensine and MAN1A1 knock out were investigated in ovarian cancer cells in vitro.RESULTS: Patients with high MAN1A1 expression in tumours showed significantly shorter RFS than those with low-MAN1A1 levels. Moreover, high MAN1A1 expression correlated significantly with advanced stage, lymph node involvement and distant metastasis. Further, the glycosylated adhesion molecule ALCAM reveals a significant adverse prognostic effect only in the presence of high MAN1A1 expression. In spheroid-formation assays, mannosidase inhibition and especially MAN1A1 knock out led to strong reduction of tumour cell aggregation.CONCLUSIONS: Our study demonstrates the unfavourable prognostic role of MAN1A1 in ovarian cancer, probably caused by an altered ability of spheroid formation, and the strong influence of this glycosylation enzyme on the prognostic impact of ALCAM.

U2 - 10.1038/s41416-019-0607-2

DO - 10.1038/s41416-019-0607-2

M3 - SCORING: Journal articles

C2 - 31659304

VL - 121

SP - 944

EP - 953

JO - BRIT J CANCER

JF - BRIT J CANCER

SN - 0007-0920

IS - 11

ER -