Advancements in investigating the role of TRAF4 in facilitating tumorigenesis and progression
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摘要: 肿瘤坏死因子受体相关因子4（tumor necrosis factor receptor-associated factor 4，TRAF4）是TRAFs（tumor necrosis factor receptor-associated factors）蛋白家族的成员之一，其作为信号转导的接头分子，具有E3泛素连接酶活性，可激活多种下游信号通路，在神经发生与胚胎发育、免疫调节与炎症反应、氧化损伤及代谢等多种生理过程中发挥着重要的调控作用。TRAF4在多种肿瘤中异常高表达，并调控肿瘤的发生发展。本文根据TRAF4的生理和病理调控功能，对TRAF4与肿瘤发生和发展的关系进行综述，为该基因在肿瘤治疗中的应用提供参考。Abstract: Tumor necrosis factor receptor-associated factor 4 (TRAF4) is a member of the TRAF protein family. As a cytoplasmic linker molecule for signal transduction and a protein with E3 ubiquitin ligase activity, TRAF4 is closely associated with various physiological processes involved in embryonic development, immune and inflammatory responses, regulation of oxidative stress injury, and metabolism. TRAF4 is highly expressed in various tumors and regulates their occurrence and development. Based on the physiological and pathological functions of TRAF4, this paper reviews the relationship between TRAF4 and tumorigenesis and provides a reference for further research regardingthe application of this gene for tumor therapy.
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表 1 TRAF4在不同类型肿瘤中的表达及肿瘤调控情况
肿瘤类型 表达/功能 主要调节分子 信号通路 功能影响 PMID 乳腺癌 高表达 PRMT5 NF-κB 促进乳腺癌细胞增殖 25704480 促癌 RSK4 AKT/ NF-κB 乳腺癌细胞的增殖、侵袭和转移 29684350 高表达 TβRI和TAK1 TGF-β 促进乳腺癌转移 23973329 高表达 SIAH1 β-catenin 促进乳腺癌细胞增殖，抑制凋亡，参与化疗药物耐药性 32671611 促癌 IRS-1 AKT 促进乳腺癌细胞增殖 33991522 高表达 p70s6k p70s6k/S6 促进乳腺癌细胞增殖 25738361 高表达 SRC-3 p53 抵抗乳腺癌细胞的凋亡 23388826 促癌 β-catenin Wnt/β-catenin 促进乳腺癌中Wnt信号通路的激活 24990246 胶质瘤 高表达 miR-29a/b/c AKT 促进胶质瘤细胞增殖，抑制凋亡 30348972 高表达 DLEU1 Hippo/Wnt 促进胶质瘤细胞增殖和迁移 31257517 高表达 CAV1 AKT/ERK1/2 胶质瘤干细胞样特性维持和TMZ耐药性 35895752 肝细胞癌 高表达 Slug和E-cadherin PI3K/AKT 促进肝癌细胞的迁移和侵袭 28256185 高表达 miR-302c-3p AKT 促进肝癌细胞转移 30087710 高表达 AKT 促进肝内胆管细胞癌细胞侵袭 29749456 肺癌 高表达 Glut1和HK2 AKT 促进肺癌细胞的葡萄糖代谢 24154876 促癌 NOX2和NOX4 NF-κB 促进NSCLC细胞ROS水平，增强NSCLC
细胞增殖和上皮间质转化28827764 高表达 MEKK3和 ERK5 EGFR 促进NSCLC细胞的增殖 35748027 25976502 促癌 ZFPM2-AS1和miR-3612 促进SCLC细胞的增殖、侵袭及肿瘤生长 32280300 前列腺癌 高表达 TrkA RTK 促进前列腺癌细胞侵袭 29715200 促癌 miR-519d-3p TGF-β 促进前列腺癌细胞增殖 29595452 促癌 miR-29a 促进转移性前列腺癌发生 24100420 子宫内膜癌 高表达 PI3K/AKT/Oct4 诱导EC细胞凋亡并抑制细胞增殖和迁移 30853613 耐药 PARP1 AKT 降低PARP1抑制剂的敏感性 32388810 结直肠癌 高表达 β-catenin、cyclinD1和c-myc Wnt/β-catenin 促进结肠癌细胞增殖、侵袭，诱导细胞凋亡 25973026 高表达 Wnt/β-catenin 促进结肠癌细胞的生长和侵袭 27842582 耐药 CHK1 ATR-TRAF4-CHK1 抑制对氟尿嘧啶和其他化学治疗剂的敏感性 32357935 鳞状细胞癌 高表达 ZFPM2-AS1 NF-κB 促进ESCC细胞增殖、迁移和侵袭，并抑制细胞凋亡 34488754 32065218 高表达 miR-21-3p 促进ESCC肿瘤干细胞的增殖和抑制凋亡 30933965 30979011 高表达 p63、p73 和 p53 促进SCCHN细胞分化 18087216 高表达 cyclinD1、c-myc、Bcl-2等 Wnt/β-catenin 促进OSCC细胞的生长、侵袭和迁移 26617938 卵巢癌 高表达 DR6 促进卵巢癌细胞迁移 30186750 高表达 YAP 促进高级别浆液性卵巢癌的恶性进展 36029535 促癌 HCG18/ miR-29a/b 促进上皮性卵巢癌细胞的增殖、迁移和上皮间质转化 34983361 骨肉瘤 高表达 AKT 促进骨肉瘤细胞增殖、集落形成，增强骨肉瘤
细胞增殖和侵袭25700355 高表达 NF-κB 促进骨肉瘤细胞增殖、细胞周期和凋亡 25270078 血液肿瘤 高表达 miR-29s和CD40 CD40/NF-κB 促进BCR信号传导和T细胞相互作用，促进CLL发生发展 33171493 促癌 CD40L和Gp39 促进MM细胞生长并抑制凋亡 10784400 促癌 E4BP4 抑制T-ALL细胞凋亡 25101525 耐药 I3C和DIM 降低T-ALL细胞化疗敏感性 22514694 PMID：PubMed唯一标识码 
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