{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTestes‐specific protease 50 (PRSS50), also known as TSP50, was originally identified as a gene normally expressed in spermatocytes, and its product exhibits structural homology to serine proteases despite possessing threonine in its catalytic site. Its expression is subject to epigenetic and transcriptional regulation, as studies have shown that DNA methylation status and promoter elements—such as Sp1 and C/EBP binding sites—modulate its basal transcription in normal testicular tissue compared to malignant tissues. These findings established TSP50 as a cancer/testis antigen with a unique enzymatic profile."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulated expression of PRSS50 has been documented in a wide variety of cancers—including breast, cervical, gastric, non‐small cell lung, and laryngocarcinoma—where its overexpression is consistently linked to enhanced tumor cell proliferation, migration, invasion, and metastatic progression. Functional studies have demonstrated that TSP50’s protease activity is integral to its oncogenic role; catalytic triad mutations impair its capacity to activate key mitogenic pathways, suggesting that cleavage events (such as the proteolytic targeting of IκBα) lead to aberrant NF‑κB signaling. Moreover, knockdown experiments in multiple cell line models have underscored its importance in driving cell cycle progression and diminishing apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistically, PRSS50 exerts its tumor‐promoting functions through several interrelated pathways. It is negatively regulated by basic fibroblast growth factor (bFGF) via ERK‐mediated phosphorylation of Sp1, and its overexpression has been shown to inhibit activin signaling—thereby reducing p27 expression and further promoting cell proliferation. In hepatocellular carcinoma, TSP50 interacts with pyruvate kinase M2 (PKM2) to increase its K433 acetylation, leading to a low pyruvate kinase activity that favors the Warburg effect. Additionally, the gene is subject to posttranscriptional regulation by microRNAs (for example, miR-4709-3p has been shown to directly target the TSP50 3’-UTR reducing its protein levels), and novel therapeutic compounds have emerged that downregulate TSP50 expression in preclinical cancer models. Elevated TSP50 expression also correlates with adverse clinicopathological features and poorer prognosis in colorectal and other cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jidong Shan, Liming Yuan, Qianxun Xiao, et al. 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