{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSerglycin (SRGN) is an intracellular chondroitin sulfate proteoglycan that has emerged as a pivotal regulator of tumor aggressiveness. Elevated SRGN expression is observed in diverse malignancies—including nasopharyngeal carcinoma, non‐small cell lung cancer, hepatocellular carcinoma, breast cancer, melanoma, and giant cell tumor of bone—where it promotes migration, invasion, and metastasis. In these tumors SRGN acts by engaging cell surface receptors (e.g., CD44) to trigger downstream signaling cascades that promote epithelial–mesenchymal transition, enhance cancer stemness, and facilitate chemoresistance. Such effects culminate in more aggressive disease and poorer clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its oncogenic roles, SRGN is crucial for immune and secretory functions. Within cytotoxic lymphocytes, SRGN complexes with granzymes to stabilize and package these apoptotic proteases, thereby facilitating their efficient transfer into target cells. In multiple myeloma, SRGN is constitutively expressed and secreted, where it mediates cell adhesion, upregulates matrix metalloproteinases, and directly interferes with the complement cascade by binding to complement components. Furthermore, SRGN is a dominant proteoglycan in endothelial cells and monocytes, playing an important role in the regulated secretion of chemokines and other signaling molecules that are essential for inflammatory and immune responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSRGN expression is also tightly regulated by the tumor microenvironment and various cellular stressors, thereby extending its influence into non–tumorigenic settings. For example, in colorectal cancer cells SRGN is upregulated by hypoxia‐inducible factor 1α, while in chondrocytes SRGN interacts with CD44 to sustain localized inflammatory responses. Elevated SRGN in nucleus pulposus cells has been linked to the progression of intervertebral disc degeneration by promoting the infiltration of pro‐inflammatory cytokines and macrophages. Collectively, these findings underscore the multifaceted role of SRGN as a mediator of intracellular protein storage, extracellular matrix interactions, and inflammation in both cancerous and noncancerous tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xin-Jian Li, Choon Kiat Ong, Yun Cao, et al. 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