3′-sialyllactose is one of the abundant components in human milk oligosaccharides (HMOs) that protect infants from various viral infections in early stages of immune system development. 3SL is a combination of lactose and sialic acid. Most sialic acids are widely expressed in animal cells and they bind to siglec proteins. In this study, we demonstrate that 3SL specifically binds to CD33. It induces megakaryocyte differentiation and subsequent apoptosis by targeting cell surface protein siglec-3 (CD33) in human chronic myeloid leukemia K562 cells. The 3SL-bound CD33 was internalized to the cytosol via caveolae-dependent endocytosis. At the molecular level, 3SL-bound CD33 recruits the suppressor of cytokine signaling 3 (SOCS3) and SH2 domain-containing protein tyrosine phosphatase 1 (SHP1). SOCS3 is degraded with CD33 by proteasome degradation, while SHP-1 activates extracellular signal–regulated kinase (ERK) to induce megakaryocytic differentiation and subsequent apoptosis. The present study, therefore, suggests that 3SL is a potential anti-leukemia agent affecting differentiation and apoptosis.

中文翻译：

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3'-唾液乳糖靶向细胞表面蛋白SIGLEC-3，并通过脂质筏依赖性内吞作用诱导巨核细胞分化和凋亡

3'-唾液乳糖是人乳寡糖（HMO）中丰富的成分之一，可在免疫系统发育的早期阶段保护婴儿免受各种病毒感染。3SL是乳糖和唾液酸的组合。大多数唾液酸在动物细胞中广泛表达，并且与siglec蛋白结合。在这项研究中，我们证明3SL特异性结合CD33。它通过靶向人类慢性粒细胞白血病K562细胞中的细胞表面蛋白siglec-3（CD33）来诱导巨核细胞分化和随后的凋亡。3SL绑定的CD33通过小窝依赖的内吞作用被内化到细胞质中。在分子水平上，与3SL结合的CD33募集细胞因子信号传导抑制因子3（SOCS3）和含SH2结构域的蛋白酪氨酸磷酸酶1（SHP1）的抑制剂。SOCS3被CD33通过蛋白酶体降解而降解，SHP-1激活细胞外信号调节激酶（ERK）诱导巨核细胞分化和随后的细胞凋亡。因此，本研究表明3SL是一种潜在的抗白血病药物，可影响分化和凋亡。