{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTspan8 has emerged as an important modulator in cancer biology. In non‐small cell lung cancer, for example, its selective enrichment on extracellular vesicles from metastatic cells is associated with increased invasion and poorer metastasis‐free survival, suggesting that Tspan8 may serve as a minimally invasive prognostic biomarker. In parallel, gene expression alterations involving Tspan8 have been observed in mouse models of endocrine neoplasia and insulinoma formation, pointing to a potential role in tumor development and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, Tspan8 functions as a valuable cell surface marker in reproductive biology by distinguishing spermatogonial stem cells from their committed progenitors. This differential expression permits the precise isolation of stem cells from heterogeneous populations, which is critical for understanding spermatogonial renewal and differentiation. In addition, mouse ablation studies have implicated Tspan8 as a potential causal gene in type 2 diabetes, with investigations assessing its impact on diverse metabolic traits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTspan8 is also involved in neuronal and intestinal physiology. In the central nervous system, a common promoter SNP is associated with reduced Tspan8 expression, with downstream transcriptome changes affecting signaling pathways relevant to psychiatric disorders such as bipolar disorder and aspects of neuronal development. Moreover, in intestinal epithelial cells, Tspan8 supports barrier integrity by coalescing with lipid rafts to regulate the endocytosis route of the interferon‑γ receptor. This action restrains Stat1 signaling and protects against inflammation, highlighting a novel role in the maintenance of intestinal homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yang Liu, Jia Fan, Ting Xu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The regulation of tetraspanin 8 gene expression-A potential new mechanism in the pathogenesis of bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.32571"}], "href": "https://doi.org/10.1002/ajmg.b.32571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28777493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28777493"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jiang Min, Shenglan Yang, Yang Cai, et al. 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