CDB25:0004299 SIGLEC15 — CD44

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Siglec-15 promotes the migration of liver cancer cells by repressing lysosomal degradation of CD44.

FEBS letters, 2021; PubMed, Homo sapiens SIGLEC15 — Homo sapiens CD44

ABSTRACT: 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.

Basic Information on SIGLEC15

Ligand Name: sialic acid binding Ig like lectin 15

Other Symbols: CD33L3, HsT1361

Ligand Location: cell membrane based on perplexity

HGNC Gene Symbol Report: SIGLEC15

GeneCards: SIGLEC15

HGNC Gene Group: Ig-like cell adhesion molecule family, Immunoglobulin superfamily domain containing

Functional Annotations for SIGLEC15

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for SIGLEC15

SIGLEC15 — ITGAM

Basic Information on CD44

Receptor Name: CD44 molecule (IN blood group)

Other Symbols: MIC4, MDU2, MDU3, IN, MC56, Pgp1, PGP-1, CD44R, HCELL, CSPG8, Hermes-1, CDw44, HUTCH-1, HUTCH-I, ECM-III, H-CAM

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: CD44

GeneCards: CD44

HGNC Gene Group: Blood group antigens, CD molecules, Proteoglycans

Functional Annotations for CD44

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for CD44

COL14A1 — CD44 ・ COL1A1 — CD44 ・ COL1A2 — CD44 ・ FGF1 — CD44 ・ FGF2 — CD44 ・ FN1 — CD44 ・ HBEGF — CD44 ・ HGF — CD44 ・ MADCAM1 — CD44 ・ MMP7 — CD44 ・ MMP9 — CD44 ・ SPP1 — CD44 ・ VCAN — CD44 ・ VIM — CD44 ・ LGALS9 — CD44 ・ SELE — CD44 ・ BGN — CD44 ・ C1QA — CD44 ・ C1QB — CD44 ・ C1QC — CD44 ・ CD6 — CD44 ・ DMP1 — CD44 ・ GPNMB — CD44 ・ LAMA5 — CD44 ・ PRG4 — CD44 ・ VEGFA — CD44