{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPRED3 is a member of the SPRED protein family, originally identified as a regulator of growth factor–induced MAP kinase activation. Like its family members SPRED1 and SPRED2, SPRED3 contains an N‐terminal EVH1 domain and a C‐terminal Sprouty-related cysteine-rich (SPR) domain that is critical for its membrane localization. However, due to the absence of a functional c-kit binding domain, SPRED3 exhibits lower inhibition of Ras/MAP kinase signaling compared with SPRED1/2. Notably, SPRED3 is expressed predominantly in the brain, underscoring a tissue‐specific role in modulating receptor-driven proliferative signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its cerebral expression, investigations into the SPRED family have indicated a broader role in the regulation of organ growth. In the liver, for instance, growth inhibitors of this family are thought to contribute to the tight control of cellular proliferation, enabling the rapid transition between cellular quiescence and growth in response to specific stimuli. Although these studies do not focus exclusively on SPRED3, the shared regulatory functions suggest that SPRED3 may also participate in maintaining tissue homeostasis in other organs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nMore recently, SPRED3 has been implicated in thyroid carcinoma, where its aberrant expression is associated with aggressive disease characteristics. Data from large-scale analyses reveal that SPRED3 is markedly upregulated in thyroid cancer tissues compared with normal thyroid tissue, with high expression levels correlating with adverse parameters such as advanced tumor stage, higher histological grade, and poor overall survival. Functional studies have demonstrated that SPRED3 overexpression enhances thyroid cancer cell viability and colony formation, an effect that is mediated in part through the activation of NF-κB signaling. Furthermore, SPRED3 appears to impact multiple molecular pathways including extracellular matrix organization, epidermal development, and receptor-mediated signaling (such as the IL-17 and PI3K-Akt pathways), while also modulating the tumor immune microenvironment by altering the infiltration profiles of various immune cells. These findings support the notion that SPRED3 may serve both as a prognostic biomarker and as a putative therapeutic target in thyroid carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Reiko Kato, Atsushi Nonami, Takaharu Taketomi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(03)00259-6"}], "href": "https://doi.org/10.1016/s0006-291x(03"}, {"type": "t", "text": "00259-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646235"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "James A J King, Niall M Corcoran, Giovanna M D'Abaco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eve-3: a liver enriched suppressor of Ras/MAPK signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2005.10.031"}], "href": "https://doi.org/10.1016/j.jhep.2005.10.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16478641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16478641"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaowei Zhang, Xiangwei Meng, Pengyun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bioinformatics analysis for the identification of Sprouty-related EVH1 domain-containing protein 3 expression and its clinical significance in thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-55187-2"}], "href": "https://doi.org/10.1038/s41598-024-55187-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38402263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38402263"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhiping Chen, Congren Wang, Mingzhu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPRED3 regulates the NF-κB signaling pathway in thyroid cancer and promotes the proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-61075-6"}], "href": "https://doi.org/10.1038/s41598-024-61075-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39227612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39227612"}]}]}]}