Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, 710069, China.
Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, 710069, China.
Biochem Biophys Res Commun. 2024 Nov 19;734:150641. doi: 10.1016/j.bbrc.2024.150641. Epub 2024 Sep 4.
Gastric cancer (GC) is one of the most aggressive and lethal diseases in the world. Cancer metastasis is the mainly leading cause of death in GC patients. Aberrant Protein O-glycosylation is closely associated with tumor occurrence and metastasis. However, the effect of aberrant O-glycosylation on the progress of GC is not completely clear. This study aimed to investigate the biological function and its underlying effects mechanism of core 1 β 1, 3-galactosyltransferase 1 (C1GALT1) C1GALT1-mediated O-glycan T antigen on GC progress. We conducted data mining analysis that C1GALT1 was obviously up-regulated in GC tissues than in para-carcinoma tissues. Elevated expression of C1GALT1 was closely associated with advanced TNM stage, lymph node metastasis, histological grade, and poor overall survival. In addition, C1GALT1 overexpression could promote GC cell proliferation, migration, and invasion, which was due to C1GALT1 overexpression-mediated O-glycan T antigen increase. Moreover, MUC1 was predicted to be a new downstream target of C1GALT1, which may be abnormally O-glycosylated by C1GALT1 thereby activating the cell adhesion signaling pathway. In conclusion, our studies proved that C1GALT1-mediated O-glycosylation increase could promote the metastasis of gastric cancer cells. These discoveries hint that C1GALT1 may serve as a novel therapeutic target for GC treatment.
胃癌（GC）是世界上最具侵袭性和致命性的疾病之一。癌症转移是 GC 患者死亡的主要原因。异常的蛋白质 O-糖基化与肿瘤的发生和转移密切相关。然而，异常 O-糖基化对 GC 进展的影响尚不完全清楚。本研究旨在探讨核心 1 β 1,3-半乳糖基转移酶 1（C1GALT1）介导的 O-聚糖 T 抗原对 GC 进展的生物学功能及其潜在作用机制。我们进行了数据挖掘分析，结果表明 C1GALT1 在 GC 组织中的表达明显高于癌旁组织。C1GALT1 的高表达与较晚的 TNM 分期、淋巴结转移、组织学分级和较差的总生存率密切相关。此外，C1GALT1 的过表达可促进 GC 细胞的增殖、迁移和侵袭，这是由于 C1GALT1 过表达介导的 O-聚糖 T 抗原增加所致。此外，预测 MUC1 是 C1GALT1 的一个新的下游靶标，它可能被 C1GALT1 异常 O-糖基化从而激活细胞黏附信号通路。总之，我们的研究证明 C1GALT1 介导的 O-糖基化增加可促进胃癌细胞的转移。这些发现提示 C1GALT1 可能成为 GC 治疗的新靶点。
