尽管大多数细胞膜蛋白都会发生糖基化修饰，但我们对蛋白质糖基化的作用和机制的理解仍然非常有限。β1,3半乳糖基转移酶（C1GalT1）是一个关键的糖基转移酶，它控制O-连接粘液型糖基核心1结构的生物合成，并在许多常见的上皮癌中过表达。本研究报告了在人类结肠癌细胞中抑制C1GalT1表达会导致细胞膜蛋白的糖基化发生显著变化，其中许多蛋白质是半乳糖结合型galectin-3和巨噬细胞半乳糖型凝集素（MGL）的配体。这导致癌细胞的增殖、粘附、迁移能力和形成肿瘤集落的能力显著降低。至关重要的是，C1GalT1抑制显著降低了galectin-3介导的肿瘤细胞间相互作用和galectin-3促进的肿瘤细胞活动。与此同时，C1GalT1抑制显著增加了MGL介导的巨噬细胞与肿瘤细胞的相互作用、巨噬细胞对肿瘤细胞的吞噬和细胞因子的分泌。植入鸡胚中的C1GalT1表达癌细胞形成的肿瘤比C1GalT1抑制的细胞形成的肿瘤显著大，并且galectin-3的存在增加了C1GalT1表达细胞的肿瘤生长，而不增加C1GalT1抑制细胞的肿瘤生长。在ME C1galt1-/-/Erb小鼠与C1galt1f/f /Erb小鼠相比，观察到更多表达MGL的巨噬细胞和树突细胞在肿瘤微环境中被吸引。这些结果表明，肿瘤细胞中C1GalT1的表达通过galectin-3和MGL介导的肿瘤细胞相互作用和肿瘤-巨噬细胞相互作用来相互控制癌症的发展和进展，对癌症的促进和免疫反应/监测的削弱具有双重影响。因此，上皮癌中C1GalT1的过表达可能代表了癌症促进的基本机制，并减弱了癌症进展中的免疫反应/监测。© 2023. 作者。

Although most cell membrane proteins are modified by glycosylation, our understanding of the role and actions of protein glycosylation is still very limited. β1,3galactosyltransferase (C1GalT1) is a key glycosyltransferase that controls the biosynthesis of the Core 1 structure of O-linked mucin type glycans and is overexpressed by many common types of epithelial cancers. This study reports that suppression of C1GalT1 expression in human colon cancer cells caused substantial changes of protein glycosylation of cell membrane proteins, many of which were ligands of the galactoside-binding galectin-3 and the macrophage galactose-type lectin (MGL). This led to significant reduction of cancer cell proliferation, adhesion, migration and the ability of tumour cells to form colonies. Crucially, C1GalT1 suppression significantly reduced galectin-3-mediated tumour cell-cell interaction and galectin-3-promoted tumour cell activities. In the meantime, C1GalT1 suppression substantially increased MGL-mediated macrophage-tumour cell interaction and macrophage-tumour cell phagocytosis and cytokine secretion. C1GalT1-expressing cancer cells implanted in chick embryos resulted in the formation of significantly bigger tumours than C1GalT1-suppressed cells and the presence of galectin-3 increased tumour growth of C1GalT1-expressing but not C1GalT1-suppressed cells. More MGL-expressing macrophages and dendritic cells were seen to be attracted to the tumour microenvironment in ME C1galt1-/-/Erb mice than in C1galt1f/f /Erb mice. These results indicate that expression of C1GalT1 by tumour cells reciprocally controls tumour cell-cell and tumour-macrophage interactions mediated by galectin-3 and MGL with double impact on cancer development and progression. C1GalT1 overexpression in epithelial cancers therefore may represent a fundamental mechanism in cancer promotion and in reduction of immune response/surveillance in cancer progression.© 2023. The Author(s).