Please use this identifier to cite or link to this item:
Title: GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells
Author: Bedia Girbés, Carmen
Badia, Miriam
Muixí, Laia
Levade, Thierry
Tauler Ferré, Romà
Sierra Jiménez, Àngels
Keywords: Metàstasi
Issue Date: 2-Oct-2019
Publisher: Nature Publishing Group
Abstract: GRP94 is an ATP-dependent chaperone able to regulate pro-oncogenic signaling pathways. Previous studies have shown a critical role of GRP94 in brain metastasis (BrM) pathogenesis and progression. In this work, an untargeted lipidomic analysis revealed that some lipid species were altered in GRP94-deficient cells, specially GM2 and GM3 gangliosides. The catalytic pathway of GM2 is affected by the low enzymatic activity of beta-Hexosaminidase (HexA), responsible for the hydrolysis of GM2 to GM3. Moreover, a deficiency of the GM2-activator protein (GM2-AP), the cofactor of HexA, is observed without alteration of gene expression, indicating a post-transcriptional alteration of GM2-AP in the GRP94-ablated cells. One plausible explanation of these observations is that GM2-AP is a client of GRP94, resulting in defective GM2 catabolic processing and lysosomal accumulation of GM2 in GRP94-ablated cells. Overall, given the role of gangliosides in cell surface dynamics and signaling, their imbalance might be linked to modifications of cell behaviour acquired in BrM progression. This work indicates that GM2-AP could be an important factor in ganglioside balance maintenance. These findings highlight the relevance of GM3 and GM2 gangliosides in BrM and reveal GM2-AP as a promising diagnosis and therapeutic target in BrM research.
Note: Reproducció del document publicat a:
It is part of: Scientific Reports, 2019-10-02, Vol. 9
Related resource:
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
BediaC.pdf3.33 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons