{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTNFRSF19, also known as TROY, is a member of the tumor necrosis factor receptor superfamily that has emerged as a key player in both oncogenic transformation and normal progenitor cell function. In melanomas, its specific expression distinguishes tumor cells from normal skin and highlights its potential as a biomarker and therapeutic target, while genome‐wide studies in nasopharyngeal carcinoma have identified TNFRSF19 as a susceptibility locus. In colorectal cancer, TNFRSF19 is transcriptionally regulated by β‐catenin, and its overexpression is associated with increased NF‑κB activity and tumor progression. Furthermore, in lung tissue cells, TNFRSF19 can protect against carcinogen‐induced transformation by competing with LRP6 for Wnt3a binding, thereby inhibiting the Wnt/β‑catenin signaling pathway."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the central nervous system and malignant gliomas, aberrant TNFRSF19 expression is linked to aggressive cell migration and invasion. Overexpression in glioma cells correlates with higher tumor grade and poor patient survival. TNFRSF19 activates Rac1 signaling via its interaction with Pyk2 and forms molecular complexes with EGFR to augment NF‑κB signaling and promote resistance to chemo‑ and radiation therapies. In addition, its intracellular signaling facilitates RhoA activation through interactions with RhoGDIα and PDZ‑RhoGEF and further stimulates the JAK1/STAT3 pathway, thereby contributing to the invasive and therapeutic‐resistant phenotype of glioblastoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumor promotion, TNFRSF19 influences normal tissue homeostasis. In hepatocellular carcinoma, reduced TNFRSF19 expression (in part due to miRNA regulation) is associated with accelerated cell proliferation and epithelial–mesenchymal transition, suggesting a tumor‐suppressive function in certain contexts. Similarly, in the gastric epithelium, TNFRSF19, together with other Wnt pathway components, participates in cellular differentiation processes. Remarkably, in the skin, TNFRSF19 serves as a marker of basal progenitor cells that drive the long‐term renewal and cornification of the interfollicular epidermis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Remco A Spanjaard, Kara M Whren, Carole Graves, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.22367"}], "href": "https://doi.org/10.1002/ijc.22367"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17187358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17187358"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jin-Xin Bei, Yi Li, Wei-Hua Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.601"}], "href": "https://doi.org/10.1038/ng.601"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20512145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20512145"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Simon Schön, Isabelle Flierman, Andrea Ofner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "β-catenin regulates NF-κB activity via TNFRSF19 in colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.28839"}], "href": "https://doi.org/10.1002/ijc.28839"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24623448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24623448"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chengcheng Deng, Yu-Xin Lin, Xue-Kang Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type I to Promote Tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-17-3205"}], "href": "https://doi.org/10.1158/0008-5472.CAN-17-3205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29735548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29735548"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xianglin Zuo, Xuchun Wang, Tingzheng Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNFRSF19 within the 13q12.12 Risk Locus Functions as a Lung Cancer Suppressor by Binding Wnt3a to Inhibit Wnt/β-Catenin Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-23-0109"}], "href": "https://doi.org/10.1158/1541-7786.MCR-23-0109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38047807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38047807"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Vincent M Paulino, Zhongbo Yang, Jean Kloss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TROY (TNFRSF19) is overexpressed in advanced glial tumors and promotes glioblastoma cell invasion via Pyk2-Rac1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-10-0334"}], "href": "https://doi.org/10.1158/1541-7786.MCR-10-0334"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20881009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20881009"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Joseph C Loftus, Harshil Dhruv, Serdar Tuncali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TROY (TNFRSF19) promotes glioblastoma survival signaling and therapeutic resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-13-0008"}], "href": "https://doi.org/10.1158/1541-7786.MCR-13-0008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23699535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23699535"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yan Lu, Xiujie Liu, Jianfeng Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TROY interacts with Rho guanine nucleotide dissociation inhibitor α (RhoGDIα) to mediate Nogo-induced inhibition of neurite outgrowth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.519744"}], "href": "https://doi.org/10.1074/jbc.M113.519744"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24129566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24129566"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zonghui Ding, Alison Roos, Jean Kloss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel Signaling Complex between TROY and EGFR Mediates Glioblastoma Cell Invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-17-0454"}], "href": "https://doi.org/10.1158/1541-7786.MCR-17-0454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29117939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29117939"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zonghui Ding, Harshil Dhruv, Aneta Kwiatkowska-Piwowarczyk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDZ-RhoGEF Is a Signaling Effector for TROY-Induced Glioblastoma Cell Invasion and Survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2018.08.008"}], "href": "https://doi.org/10.1016/j.neo.2018.08.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30219706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30219706"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zonghui Ding, Jean M Kloss, Serdar Tuncali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TROY signals through JAK1-STAT3 to promote glioblastoma cell migration and resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2020.06.005"}], "href": "https://doi.org/10.1016/j.neo.2020.06.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32629176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32629176"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kai Kretzschmar, Kim E Boonekamp, Margit Bleijs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Troy/Tnfrsf19 marks epidermal cells that govern interfollicular epidermal renewal and cornification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Reports (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stemcr.2021.07.007"}], "href": "https://doi.org/10.1016/j.stemcr.2021.07.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34358453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34358453"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "LiMing Guo, Rui Gao, JianChen Gan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of TNFRSF19 and RAB43 by a novel miRNA, miR-HCC3, promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2020.02.105"}], "href": "https://doi.org/10.1016/j.bbrc.2020.02.105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32102752"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32102752"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Samaneh Saberi, Abbas Piryaei, Esmat Mirabzadeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunohistochemical Analysis of LGR5 and TROY Expression in Gastric Carcinogenesis Demonstrates an Inverse Trend"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Iran Biomed J (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30501144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30501144"}]}]}]}