{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNT5DC2 has emerged as an important oncogenic factor in several malignancies. In glioblastoma, NT5DC2 is preferentially expressed in glioma stem‐like cells and plays a key role in tumor initiation by upregulating the proto‐oncogene Fyn, thereby promoting aggressive tumor growth and resistance to conventional therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn hepatocellular carcinoma, overexpression of NT5DC2 was found to correlate with larger tumors, vascular invasion, and poor survival. Mechanistically, NT5DC2 binds directly to the epidermal growth factor receptor (EGFR), reducing its ubiquitination and degradation. This stabilization of EGFR enhances downstream signaling that drives cell proliferation, clonogenicity, and tumor growth; interestingly, inhibition of EGFR with erlotinib abrogated these protumor effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn non‐small cell lung cancer, NT5DC2 is significantly upregulated relative to normal tissue, where its overexpression promotes cell proliferation, migration, and invasion while inhibiting apoptosis. These effects are mediated, at least in part, through the suppression of p53 expression. Conversely, NT5DC2 knockdown leads to cell cycle arrest (notably at the G2 phase) and enhanced apoptotic cell death in a p53‐dependent manner, underscoring its potential role as a driver of tumorigenesis in NSCLC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn colorectal cancer, NT5DC2 expression is markedly elevated and is associated with poor overall survival. Functionally, NT5DC2 promotes tumor progression by activating a VEGF‐mediated axis that increases angiogenesis and facilitates tumor‐associated macrophage recruitment via upregulation of HIF‑1α, VEGF‑A, and the CCL2/CCR2 signaling pathway. Depletion of NT5DC2 in vitro and in vivo results in reduced proliferation, migration, invasion, and metastasis, highlighting its contribution to CRC development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn diffuse large B‑cell lymphoma, NT5DC2 contributes to malignant cell growth by modulating the p53 signaling pathway. NT5DC2 knockdown not only suppresses cell viability and proliferation but also induces cell cycle arrest and promotes apoptosis. Furthermore, functional interplay between NT5DC2 and IGF2BP2 was observed, where overexpression of IGF2BP2 reversed the inhibitory effects of NT5DC2 downregulation on key regulators such as p53 and p21."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPreliminary observations in gastric cancer have prompted interest in NT5DC2 as a potential prognostic marker, particularly in the context of metastatic disease where early diagnosis remains challenging and outcomes are typically poor. Although detailed functional insights are still emerging for this tumor type, NT5DC2 is being explored for its ability to inform prognosis and possibly guide therapeutic decisions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn triple‐negative breast cancer, NT5DC2 is significantly upregulated and interacts with EGFR to activate downstream signaling pathways that support malignant progression. Its overexpression enhances glycolytic metabolism, as indicated by increased extracellular acidification, ATP production, lactic acid production, and glucose uptake, leading to enhanced proliferation, migration, and invasion. Moreover, NT5DC2 influences the tumor microenvironment by promoting M2 macrophage polarization, which may contribute to neuropathic pain associated with this aggressive subtype. Importantly, silencing NT5DC2 mitigates these effects, and reactivation of EGFR signaling reverses the beneficial impact of NT5DC2 knockdown."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Saisai Guo, Haowen Ran, Dake Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2019.04.003"}], "href": "https://doi.org/10.1016/j.canlet.2019.04.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30978441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30978441"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kang-Shuai Li, Xiao-Dong Zhu, Hong-Da Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NT5DC2 promotes tumor cell proliferation by stabilizing EGFR in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-2549-2"}], "href": "https://doi.org/10.1038/s41419-020-2549-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32382041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32382041"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiang Jin, Xingang Liu, Zhen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NT5DC2 suppression restrains progression towards metastasis of non-small-cell lung cancer through regulation p53 signaling."}]}, {"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.2020.06.139"}], "href": "https://doi.org/10.1016/j.bbrc.2020.06.139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32962856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32962856"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhenyu Zhu, Qingsheng Hou, Hongliang Guo "}, {"type": "b", "children": [{"type": "t", "text": "NT5DC2 knockdown inhibits colorectal carcinoma progression by repressing metastasis, angiogenesis and tumor-associated macrophage recruitment: A mechanism involving VEGF signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2020.112311"}], "href": "https://doi.org/10.1016/j.yexcr.2020.112311"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32991874"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32991874"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuying Cui, Yu Wen, Chao Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased RNA‑binding protein IGF2BP2 downregulates NT5DC2, which suppresses cell proliferation, and induces cell cycle arrest and apoptosis in diffuse large B‑cell lymphoma cells by regulating the p53 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2022.12802"}], "href": "https://doi.org/10.3892/mmr.2022.12802"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35894142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35894142"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rula Sha, Jiaming Zhang, Fanjie Meng, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "NT5DC2 knockdown suppresses progression, glycolysis, and neuropathic pain in triple-negative breast cancer by blocking the EGFR pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.23688"}], "href": "https://doi.org/10.1002/mc.23688"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38289126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38289126"}]}]}]}