{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLEC3A is a cartilage‐derived C‐type lectin with multifaceted roles in extracellular matrix organization and cell–matrix interactions. Initially identified as a homolog of tetranectin with a predicted trimeric structure, CLEC3A is expressed preferentially in cartilage yet is also detectable in various tumor types, including breast and colon cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cartilage, CLEC3A interacts with extracellular matrix components by binding heparan sulfate proteoglycans, thereby enhancing cell adhesion to integrin ligands such as laminin‑332 and fibronectin; however, proteolytic cleavage by matrix metalloproteinase‑7 yields fragments that lose this adhesive function, suggesting a regulatory mechanism in tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Furthermore, CLEC3A binds plasminogen and augments tissue plasminogen activator–mediated plasminogen activation, implicating it in proteolytic cascades that contribute to matrix turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, particularly breast invasive ductal carcinoma, elevated CLEC3A expression correlates with increased tumor proliferation, enhanced migratory and invasive capabilities via activation of PI3K/Akt signaling, and ultimately poorer clinical outcomes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Conversely, lower expression levels have been associated with favorable survival, as supported by independent prognostic evaluations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In osteoarthritis, CLEC3A emerges as a novel biomarker of cartilage degradation; its expression is upregulated upon interleukin‑1α stimulation and contributes to matrix breakdown, while autoantibodies targeting CLEC3A are detectable in patient sera, further underscoring its clinical relevance in disease diagnosis and potentially in delineating osteoarthritis subgroups."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Notably, peptides derived from CLEC3A have been shown to possess antimicrobial activity against Gram‐negative and Gram‐positive bacteria by binding lipopolysaccharide and lipoteichoic acid and disrupting bacterial membranes, which points to additional therapeutic applications, for instance in the prevention of septic arthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight CLEC3A as a multifunctional protein that not only orchestrates extracellular matrix organization and plasminogen activation in cartilage but also modulates cell adhesion, influences tumor progression via oncogenic signaling pathways, and may serve as a promising biomarker or therapeutic target in osteoarthritis and infectious conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "P J Neame, H Tapp, D R Grimm "}, {"type": "b", "children": [{"type": "t", "text": "The cartilage-derived, C-type lectin (CLECSF1): structure of the gene and chromosomal location."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0167-4781(99)00087-1"}], "href": "https://doi.org/10.1016/s0167-4781(99"}, {"type": "t", "text": "00087-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10524194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10524194"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jun Tsunezumi, Shouichi Higashi, Kaoru Miyazaki "}, {"type": "b", "children": [{"type": "t", "text": "Matrilysin (MMP-7) cleaves C-type lectin domain family 3 member A (CLEC3A) on tumor cell surface and modulates its cell adhesion activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22062"}], "href": "https://doi.org/10.1002/jcb.22062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19173304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19173304"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daniela Lau, Dzemal Elezagic, Gabriele Hermes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator-mediated plasminogen activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M117.818930"}], "href": "https://doi.org/10.1074/jbc.M117.818930"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29146595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29146595"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jun Ni, Yun Peng, Fu-Lan Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Onco Targets Ther (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/OTT.S161311"}], "href": "https://doi.org/10.2147/OTT.S161311"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29892197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29892197"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chong Ren, Runsang Pan, Lisong Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2020.10986"}], "href": "https://doi.org/10.3892/mmr.2020.10986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32319617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32319617"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xingfeng Chen, Yujing Wang, Yue Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of immune-related cells and genes in the breast invasive carcinoma microenvironment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.203879"}], "href": "https://doi.org/10.18632/aging.203879"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35120331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35120331"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "C Karlsson, T Dehne, A Lindahl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Osteoarthritis Cartilage (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.joca.2009.12.002"}], "href": "https://doi.org/10.1016/j.joca.2009.12.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20060954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20060954"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Johannes Ruthard, Gabriele Hermes, Ursula Hartmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of antibodies against extracellular matrix proteins in human osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.07.036"}], "href": "https://doi.org/10.1016/j.bbrc.2018.07.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30001809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30001809"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "D Elezagic, M Mörgelin, G Hermes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antimicrobial peptides derived from the cartilage.-specific C-type Lectin Domain Family 3 Member A (CLEC3A) - potential in the prevention and treatment of septic arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Osteoarthritis Cartilage (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.joca.2019.06.007"}], "href": "https://doi.org/10.1016/j.joca.2019.06.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31279936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31279936"}]}]}]}