Deschuyter Marlène, Leger David Yannick, Verboom Anne, Chaunavel Alain, Maftah Abderrahman, Petit Jean-Michel
PEIRENE Laboratory, EA 7500, Glycosylation and Cell Differentiation, Faculty of Sciences and Technology, University of Limoges Limoges F-87060, France.
PEIRENE Laboratory, EA 7500, Faculty of Pharmacy, University of Limoges Limoges 87025, France.
Am J Cancer Res. 2022 Jan 15;12(1):280-302. eCollection 2022.
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 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 by specific shRNA, and then characterized these cells by performing functional tests. We found that knock down (KD) significantly decreases tumor cell proliferation, cell migration and invasiveness properties . The cell cycle of these cells is affected with a change in cell cycle distribution and an increase of cell apoptosis. The effect of KD was then studied , 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.
肿瘤细胞具有修饰的糖基化谱，这促进了它们在肿瘤中的进化和/或维持。唾液酸化是一种在癌症中经常发生改变的糖基化类型。RNA测序数据库分析显示，唾液酸转移酶基因在结直肠癌（CRC）的所有阶段均显著过表达。ST3GAL2对糖蛋白和糖脂都进行唾液酸化修饰。这项工作的目的是研究ST3GAL2在结直肠癌中的作用。使用源自结直肠癌II期的HT29肿瘤细胞系，我们通过特异性短发夹RNA（shRNA）降低了其表达，然后通过进行功能测试对这些细胞进行表征。我们发现敲低（KD）显著降低了肿瘤细胞的增殖、细胞迁移和侵袭特性。这些细胞的细胞周期受到影响，细胞周期分布发生变化，细胞凋亡增加。然后在将肿瘤细胞异种移植到裸鼠体内后研究了KD的作用，结果显示肿瘤进展显著降低。这项工作表明，ST3GAL2通过修饰有待具体鉴定的糖蛋白和糖脂的唾液酸化状态，在结直肠肿瘤细胞的行为中起主要作用。
