Siglec-15 promotes the migration of liver cancer cells by repressing lysosomal degradation of CD44.
CD44
Sialic acids
Siglec-15
migration
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
14
06
2021
received:
20
03
2021
accepted:
14
07
2021
pubmed:
31
7
2021
medline:
28
9
2021
entrez:
30
7
2021
Statut:
ppublish
Résumé
Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as a novel potential target for cancer immunotherapy. Here, we explored the role of Siglec-15 in human hepatoma cells. In this study, we found that the expression of Siglec-15 is substantially upregulated in liver cancer tissues in comparison with the nontumor tissues. Functionally, in vitro experiments show that Siglec-15 promotes the migration of hepatoma cells. Furthermore, the data demonstrated an interaction between Siglec-15 and CD44, a transmembrane glycoprotein that mediates tumor progression and metastasis. In addition, we show that CD44 is modified by α2,6-linked sialic acids on N-glycans in hepatoma cells and that CD44 sialylation affects its interaction with Siglec-15. Removal of the sialic acid residues from CD44 resulted in suppressed interaction between Siglec-15 and CD44. We further demonstrate that Siglec-15 interacts and promotes the stability of CD44 by preventing its lysosomal-mediated degradation. Taken together, our findings demonstrate that Siglec-15 promotes the migration of hepatoma cells by regulating the CD44 protein stability.
Identifiants
pubmed: 34328657
doi: 10.1002/1873-3468.14169
doi:
Substances chimiques
CD44 protein, human
0
Hyaluronan Receptors
0
Immunoglobulins
0
Membrane Proteins
0
SIGLEC15 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2290-2302Informations de copyright
© 2021 Federation of European Biochemical Societies.
Références
Saeki I, Yamasaki T, Maeda M, Hisanaga T, Iwamoto T, Fujisawa K, Matsumoto T, Hidaka I, Marumoto Y, Ishikawa T et al. (2018) Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy. World J Hepatol 10, 571-584.
Darvin P, Toor SM, Sasidharan Nair V and Elkord E (2018) Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 50, 1-11.
El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling THR et al. (2017) Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 389, 2492-2502.
Xu F, Jin T, Zhu Y and Dai C (2018) Immune checkpoint therapy in liver cancer. J Exp Clin Cancer Res 37, 110.
Qin S, Xu L, Yi M, Yu S, Wu K and Luo S (2019) Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol Cancer 18, 155.
Ribas A (2015) Adaptive immune resistance: how cancer protects from immune attack. Cancer Discov 5, 915-919.
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X et al. (2019) Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat Med 25, 656-666.
(2020) Siglec-15: an attractive immunotherapy target. Cancer Discov 10, 7-8.
Angata T (2020) Siglec-15: a potential regulator of osteoporosis, cancer, and infectious diseases. J Biomed Sci 27, 10.
Angata T, Tabuchi Y, Nakamura K and Nakamura M (2007) Siglec-15: an immune system Siglec conserved throughout vertebrate evolution. Glycobiology 17, 838-846.
Macauley MS, Crocker PR and Paulson JC (2014) Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol 14, 653-666.
Sun J, Lu Q, Sanmamed MF and Wang J (2021) Siglec-15 as an emerging target for next-generation cancer immunotherapy. Clin Cancer Res 27, 680-688.
Wei Y, Jiang Y, Zou F, Liu Y, Wang S, Xu N, Xu W, Cui C, Xing Y, Liu Y et al. (2013) Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells. Proc Natl Acad Sci USA 110, 6829-6834.
Ma L, Hernandez MO, Zhao Y, Mehta M, Tran B, Kelly M, Rae Z, Hernandez JM, Davis JL, Martin SP et al. (2019) Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell 36, e6.
Li Z, Liu Y, Tuve S, Xun Y, Fan X, Min L, Feng Q, Kiviat N, Kiem HP, Disis ML et al. (2009) Toward a stem cell gene therapy for breast cancer. Blood 113, 5423-5433.
Briard JG, Jiang H, Moremen KW, Macauley MS and Wu P (2018) Cell-based glycan arrays for probing glycan-glycan binding protein interactions. Nat Commun 9, 880.
Chen C, Zhao S, Karnad A and Freeman JW (2018) The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol 11, 64.
Liu X, Taftaf R, Kawaguchi M, Chang YF, Chen W, Entenberg D, Zhang Y, Gerratana L, Huang S, Patel DB et al. (2019) Homophilic CD44 interactions mediate tumor cell aggregation and polyclonal metastasis in patient-derived breast cancer models. Cancer Discov 9, 96-113.
Chaffer CL and Goetz JG (2018) CD44 orchestrates metastatic teamwork. Dev Cell 47, 691-693.
Veland N, Lu Y, Hardikar S, Gaddis S, Zeng Y, Liu B, Estecio MR, Takata Y, Lin K, Tomida MW et al. (2019) DNMT3L facilitates DNA methylation partly by maintaining DNMT3A stability in mouse embryonic stem cells. Nucleic Acids Res 47, 152-167.
Rubinsztein DC (2006) The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443, 780-786.
Cheng J, Wang R, Zhong G, Chen X, Cheng Y, Li W and Yang Y (2020) ST6GAL2 downregulation inhibits cell adhesion and invasion and is associated with improved patient survival in breast cancer. Onco Targets Ther 13, 903-914.
Laubli H and Varki A (2020) Sialic acid-binding immunoglobulin-like lectins (Siglecs) detect self-associated molecular patterns to regulate immune responses. Cell Mol Life Sci 77, 593-605.
Rodrigues E, Jung J, Park H, Loo C, Soukhtehzari S, Kitova EN, Mozaneh F, Daskhan G, Schmidt EN, Aghanya V et al. (2020) A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands. Nat Commun 11, 5091.
Lubbers J, Rodriguez E and van Kooyk Y (2018) Modulation of Immune Tolerance via Siglec-Sialic Acid Interactions. Front Immunol 9, 2807.
Hiruma Y, Hirai T and Tsuda E (2011) Siglec-15, a member of the sialic acid-binding lectin, is a novel regulator for osteoclast differentiation. Biochem Biophys Res Commun 409, 424-429.
Nitschke L (2014) CD22 and Siglec-G regulate inhibition of B-cell signaling by sialic acid ligand binding and control B-cell tolerance. Glycobiology 24, 807-817.
Meril S, Harush O, Reboh Y, Matikhina T, Barliya T and Cohen CJ (2020) Targeting glycosylated antigens on cancer cells using siglec-7/9-based CAR T-cells. Mol Carcinog 59, 713-723.
Takamiya R, Ohtsubo K, Takamatsu S, Taniguchi N and Angata T (2013) The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-beta secretion from monocytes/macrophages through the DAP12-Syk pathway. Glycobiology 23, 178-187.
Murugesan G, Correia VG, Palma AS, Chai W, Li C, Feizi T, Martin E, Laux B, Franz A, Fuchs K et al. (2021) Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression. Glycobiology 31, 44-54.