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

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Abstract

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.

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Acknowledgements

This study has been in part supported by the Basic Science Research Program through National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of Korea (NRF-2015R1D1A1A01057153).

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Authors and Affiliations

  1. Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi-Do, 440-746, South Korea

    Sun-Hyung Ha, Jun-Young Park, Fukushi Abekura & Cheorl-Ho Kim

  2. School of Korean Medicine, Healthy Aging Korean Medical Research Center, Pusan National University, Yangsan, Gyeongsangnam-do, 50612, Republic of Korea

    Choong-Hwan Kwak & Tae-Wook Chung

  3. Faculty of Medicinal Biotechnology, Dong-A University, Busan, Republic of Korea

    Young-Choon Lee

  4. Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju, 54896, South Korea

    Jong-suk Kim

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  1. Sun-Hyung Ha
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Contributions

S.H.H designed and performed most of experiments and wrote the manuscript. C.H.K (Choong-Hwan Kwak), J.Y.P, F.A performed experiments. Y.C.L, J.S.K, T.W.C and C.H.K (Cheorl-Ho Kim) contributed reagents/ materials/analysis tools, designed and supervised this paper.

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Correspondence to Tae-Wook Chung or Cheorl-Ho Kim.

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Ha, SH., Kwak, CH., Park, JY. et al. 3′-sialyllactose targets cell surface protein, SIGLEC-3, and induces megakaryocyte differentiation and apoptosis by lipid raft-dependent endocytosis. Glycoconj J 37, 187–200 (2020). https://doi.org/10.1007/s10719-019-09902-1

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