3′-sialyllactose targets cell surface protein, SIGLEC-3, and induces megakaryocyte differentiation and apoptosis by lipid raft-dependent endocytosis

• Published in: Glycoconjugate journal Vol. 37; no. 2; pp. 187 - 200
• Main Authors: Ha, Sun-Hyung, Kwak, Choong-Hwan, Park, Jun-Young, Abekura, Fukushi, Lee, Young-Choon, Kim, Jong-suk, Chung, Tae-Wook, Kim, Cheorl-Ho
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2020; Springer Nature B.V
• Subjects: Apoptosis; Biochemistry; Biomedical and Life Sciences; Breast milk; Caveolae; Cell Differentiation; Cell surface; Chronic myeloid leukemia; Cytosol; Endocytosis; Extracellular signal-regulated kinase; HCT116 Cells; HEK293 Cells; HeLa Cells; Humans; Immune system; Infants; K562 Cells; Lactose; Leukemia; Life Sciences; Megakaryocytes - cytology; Megakaryocytes - metabolism; Membrane Microdomains - metabolism; Myeloid leukemia; Oligosaccharides; Oligosaccharides - metabolism; Original Article; Pathology; Proteasomes; Protein Binding; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism; Protein-tyrosine-phosphatase; Proteins; Proteolysis; SHP-1 protein; Sialic Acid Binding Ig-like Lectin 3 - metabolism; Sialic acids; SOCS-3 protein; Suppressor of Cytokine Signaling 3 Protein - metabolism; SIGLEC-3; 3′-sialyllactose; Chronic myeloid leukemia; Differentiation; CD33; Cancer; Apoptosis
• ISSN: 0282-0080; 1573-4986; 1573-4986
• DOI: 10.1007/s10719-019-09902-1

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.