{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ADAM‐like Decysin‐1 (ADAMDEC1) is an atypical, secreted metalloprotease with unique biochemical features—including an unusual zinc‐binding active site that employs an aspartic acid residue instead of a histidine—which enable it to evade inhibition by conventional metalloprotease inhibitors (e.g. TIMP‐3)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Originally identified as a novel member of the ADAM family with a truncated domain structure compared with classical ADAM proteins, ADAMDEC1 is expressed predominantly by cells of the innate immune system (such as dendritic cells and macrophages) and can be regulated by inflammatory signaling pathways including MAP kinases and NFκB."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In inflammatory and immune-mediated diseases, ADAMDEC1 expression is dynamically modulated. For example, its marked upregulation in lung tissues correlates with disease severity and may contribute to lung damage and remodeling in sarcoidosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in the gastrointestinal tract, ADAMDEC1 has been implicated in maintaining colon epithelial integrity during colitis and protecting against bacterial insults in Crohn’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, in conditions such as rosacea, elevated ADAMDEC1 levels in M1‐polarized macrophages potentiate local inflammation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and its upregulation is also observed in monocytes from patients with systemic lupus erythematosus, underscoring a role in modulating immune cell activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its functions in immune regulation and tissue remodeling, ADAMDEC1 plays context‐dependent roles in cancer. In certain malignancies such as glioblastoma and non‐small cell lung cancer, ADAMDEC1 is upregulated and contributes to oncogenic signaling—either by establishing a positive feedback loop that releases and activates FGF2 to maintain cancer stem cell properties"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "or by engaging the PI3K/AKT pathway to promote proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In contrast, in epithelial contexts ADAMDEC1 secreted by normal cells can facilitate the apical extrusion of neighboring transformed cells by modulating cytoskeletal regulators such as filamin, thereby contributing to an intrinsic anticancer mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, ADAMDEC1 expression is altered during tumorigenesis in colorectal cancer and adenoma, where decreased expression is observed during tumor progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and its differential regulation has been noted in unstable atherosclerotic plaques, suggesting a possible contribution to extracellular matrix reorganization and plaque destabilization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Furthermore, emerging roles in placental development have been indicated by findings that ADAMDEC1 promotes trophoblast differentiation, with potential implications for preeclampsia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, ADAMDEC1 functions as a multifaceted mediator at the interface of innate immunity, tissue remodeling, and cancer biology. Its proteolytic activity, regulated expression in immune cells and responsiveness to inflammatory stimuli enable it to act both as a modulator of immune responses and as a facilitator of cellular processes such as growth factor activation and extracellular remodeling. Thus, ADAMDEC1 represents a promising candidate as a biomarker and therapeutic target in diverse pathological conditions ranging from inflammatory diseases and autoimmunity to cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jacob Lund, Linda Troeberg, Henrik Kjeldal, et al. 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