Role of Sialyl-O-Acetyltransferase CASD1 on GD2 Ganglioside O-Acetylation in Breast Cancer Cells.

Sumeyye Cavdarli,Martina Mühlenhoff,Jean-Marc Le Doussal,Malena Albers,Sophie Groux-Degroote,Philippe Delannoy,Dorothée Vicogne,Anna-Maria Baumann,Larissa Schröter

doi:10.3390/cells10061468

Abstract

The O-acetylated form of GD2, almost exclusively expressed in cancerous tissues, is considered to be a promising therapeutic target for neuroectoderm-derived tumors, especially for breast cancer. Our recent data have shown that 9-O-acetylated GD2 (9-OAcGD2) is the major O-acetylated ganglioside species in breast cancer cells. In 2015, Baumann et al. proposed that Cas 1 domain containing 1 (CASD1), which is the only known human sialyl-O-acetyltransferase, plays a role in GD3 O-acetylation. However, the mechanisms of ganglioside O-acetylation remain poorly understood. The aim of this study was to determine the involvement of CASD1 in GD2 O-acetylation in breast cancer. The role of CASD1 in OAcGD2 synthesis was first demonstrated using wild type CHO and CHOΔCasd1 cells as cellular models. Overexpression using plasmid transfection and siRNA strategies was used to modulate CASD1 expression in SUM159PT breast cancer cell line. Our results showed that OAcGD2 expression was reduced in SUM159PT that was transiently depleted for CASD1 expression. Additionally, OAcGD2 expression was increased in SUM159PT cells transiently overexpressing CASD1. The modulation of CASD1 expression using transient transfection strategies provided interesting insights into the role of CASD1 in OAcGD2 and OAcGD3 biosynthesis, and it highlights the importance of further studies on O-acetylation mechanisms.

Highlights

IntroductionGangliosides are acidic glycosphingolipids carrying one or more sialic acid residues in their carbohydrate moiety, and they are mainly located in lipid rafts at the outer leaflet of the plasma membrane [5]
We have previously shown that GD2 interacts with c-Met tyrosine kinase receptor in MDA-MB-231 breast cancer (BC) cells and it induces the activation of PI3K/Akt and MEK/ERK signaling pathways [9]
CASD1 is the only human SOAT known up to date, which is involved in the O-acetylation of GD3 ganglioside [25]

Summary

Introduction

Gangliosides are acidic glycosphingolipids carrying one or more sialic acid residues in their carbohydrate moiety, and they are mainly located in lipid rafts at the outer leaflet of the plasma membrane [5]. They are found in different cell types as a mixture of di-, tri-, and tetra- saccharide structures, which confers to gangliosides a high structural heterogeneity [6]. The biosynthesis of GD2 is very well described, but its mechanism of

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