{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Epidermal growth factor–like domain 8 (EGFL8) is a relatively newly characterized protein that belongs to the EGFL family and is a paralog of EGFL7."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Initial studies identified EGFL8 in endothelial cells with a domain structure similar to that of EGFL7, suggesting that it might share related biological roles.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the peripheral nervous system, EGFL8 has been discovered as a matricellular protein with neuritogenic activity. Specifically, it promotes neurite outgrowth and rewires cellular signaling by activating kinases that are involved in neurogenesis, hinting at a potential role in nerve repair and regeneration processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer biology, several studies have demonstrated that EGFL8 expression is significantly reduced in a range of gastrointestinal tumors. In gastric cancer, diminished EGFL8 levels correlate with peritoneal dissemination and advanced tumor stage"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while in colorectal cancer, down‐regulation of EGFL8 is associated with distant metastasis, higher TNM stage, and poorer patient survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in hepatocellular carcinoma, lower EGFL8 expression correlates with aggressive features such as multiple nodules, vascular invasion, and advanced disease, with functional studies suggesting that EGFL8 suppresses cancer cell migration and invasion—possibly through modulation of the Notch signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in the nervous system and tumor suppression, EGFL8 appears to significantly influence immune cell development. Experiments in mice have shown that administration of recombinant EGFL8 reduces thymus weight, inhibits thymocyte proliferation, and induces apoptosis. Moreover, EGFL8 negatively regulates Notch signaling in both thymocytes and thymic epithelial cells (TECs), thereby modulating cell adhesion properties and influencing the maturation of T cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Complementary expression analyses in mouse tissues further reveal that EGFL8 is broadly expressed, consistent with its multifaceted roles in different organ systems."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, current evidence indicates that EGFL8 functions as a modulatory protein with diverse roles: it facilitates neurite outgrowth in nerve repair, acts as a potential tumor suppressor in various gastrointestinal malignancies, and serves as a negative regulator of T‐cell development via Notch pathway modulation in the thymus. These findings not only enhance our understanding of EGFL8’s biological activities but also may pave the way for its application as a prognostic biomarker or therapeutic target in both oncology and immunology.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael J Fitch, Luisa Campagnolo, Frank Kuhnert, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of EGFL8: a novel biomarker for advanced gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2011)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21965749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21965749"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fan Wu, Atsushi Shirahata, Kazuma Sakuraba, et al. 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