Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation
Menée à partir d'échantillons tumoraux prélevés sur 204 patientes atteintes d'un cancer de l'ovaire et menée sur des lignées cellulaires, cette étude évalue l'association entre le niveau d'expression de la mannosidase MAN1A1 et le pronostic, puis analyse l'effet de la N-glycosylation liée à MAN1A1 sur l'agrégation des cellules tumorales et le rôle pronostique des molécules d'adhésion ICAM-I et ALCAM
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.
British Journal of Cancer , résumé, 2018