ST3GAL2 knock-down decreases tumoral character of colorectal cancer cells in vitro and in vivo

Marlène Deschuyter; David Yannick Leger; Anne Verboom; Alain Chaunavel; Abderrahman Maftah; Jean-Michel Petit

ST3GAL2 knock-down decreases tumoral character of colorectal cancer cells in vitro and in vivo

Am J Cancer Res. 2022 Jan 15;12(1):280-302. eCollection 2022.

Authors

Marlène Deschuyter¹, David Yannick Leger², Anne Verboom¹, Alain Chaunavel³, Abderrahman Maftah¹, Jean-Michel Petit¹

Affiliations

¹ PEIRENE Laboratory, EA 7500, Glycosylation and Cell Differentiation, Faculty of Sciences and Technology, University of Limoges Limoges F-87060, France.
² PEIRENE Laboratory, EA 7500, Faculty of Pharmacy, University of Limoges Limoges 87025, France.
³ Department of Pathology, Limoges University Hospital Limoges 87042, France.

PMID: 35141018
PMCID: PMC8822282

Abstract

Tumor cells have a modified glycosylation profile that promotes their evolution and/or their maintenance in the tumor. Sialylation is a type of glycosylation that is often altered in cancers. RNA-Seq database analysis revealed that the sialyltransferase gene ST3GAL2 is significantly overexpressed at all stages of colorectal cancer (CRC). ST3GAL2 sialylates both glycoproteins and glycolipids. The aim of this work was to investigate the involvement of ST3GAL2 in CRC. Using the HT29 tumor cell line derived from a stage II of CRC, we decreased the expression of ST3GAL2 by specific shRNA, and then characterized these cells by performing functional tests. We found that ST3GAL2 knock down (KD) significantly decreases tumor cell proliferation, cell migration and invasiveness properties in vitro. The cell cycle of these cells is affected with a change in cell cycle distribution and an increase of cell apoptosis. The effect of ST3GAL2 KD was then studied in vivo, following xenografts into nude mice, in which the tumor progression was significantly reduced. This work demonstrates that ST3GAL2 is a major player in the behavior of colorectal tumor cells, by modifying the sialylation state of glycoproteins and glycolipids which remain to be specifically identified.

Keywords: HT29; ST3GAL2; biopsies; colorectal cancer; xenografts.