DLGAP5,也称为Disks large-associated protein 5,是一种微管相关蛋白,参与调控细胞周期和细胞增殖[1]。DLGAP5在多种癌症中表达上调,并与不良预后相关[2]。DLGAP5通过与E2F1结合,稳定E2F1并促进其转录,形成正反馈循环,从而促进膀胱癌的发生和发展[1]。此外,DLGAP5还可以通过上调PLK1的表达促进肺癌的生长[2]。DLGAP5还参与调控乳腺癌细胞的增殖、迁移、侵袭和细胞周期,通过JAK2/STAT3信号通路发挥作用[3]。DLGAP5在多囊卵巢综合征(PCOS)中表达上调,抑制细胞凋亡并促进细胞增殖[4]。DLGAP5还与COVID-19和HIV的相互作用相关,可能成为HIV感染COVID-19患者的潜在治疗靶点[5]。DLGAP5在胆囊癌中表达上调,并通过激活cAMP途径促进胆囊癌细胞的迁移和肿瘤相关巨噬细胞M2极化[6]。DLGAP5在子宫内膜癌中表达上调,并通过激活Wnt/β-catenin信号通路促进子宫内膜癌细胞的恶性表型[7]。DLGAP5在肺癌中表达上调,通过调节细胞周期促进肺癌细胞增殖,并与不良预后和免疫治疗反应相关[8]。DLGAP5在乳腺癌中表达上调,与不良预后相关,可能成为乳腺癌的潜在生物标志物和治疗靶点[9]。DLGAP5在前列腺癌中与雄激素受体相关,与化疗药物docetaxel具有协同作用,可能成为前列腺癌治疗的潜在靶点[10]。
综上所述,DLGAP5是一种重要的微管相关蛋白,参与调控细胞周期和细胞增殖。DLGAP5在多种癌症中表达上调,并与不良预后相关。DLGAP5通过多种机制促进肿瘤的发生和发展,包括与E2F1结合、上调PLK1表达、调控JAK2/STAT3信号通路、抑制细胞凋亡、激活cAMP途径、激活Wnt/β-catenin信号通路等。DLGAP5的研究有助于深入理解肿瘤发生和发展的机制,为癌症的治疗和预防提供新的思路和策略。
参考文献:
1. Zhou, Fenfang, Deng, Zhao, Shen, Dexin, Ju, Lingao, Wang, Xinghuan. 2024. DLGAP5 triggers proliferation and metastasis of bladder cancer by stabilizing E2F1 via USP11. In Oncogene, 43, 594-607. doi:10.1038/s41388-023-02932-y. https://pubmed.ncbi.nlm.nih.gov/38182895/
2. Chen, Maojian, Zhang, Shaoping, Wang, Fan, Jiang, Wei, Zhang, Li. 2024. DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target. In Journal of translational medicine, 22, 209. doi:10.1186/s12967-024-04910-8. https://pubmed.ncbi.nlm.nih.gov/38414025/
3. Li, Yujie, Wei, Jie, Sun, Yao, Zhang, Huan, Jin, Tianbo. 2023. DLGAP5 Regulates the Proliferation, Migration, Invasion, and Cell Cycle of Breast Cancer Cells via the JAK2/STAT3 Signaling Axis. In International journal of molecular sciences, 24, . doi:10.3390/ijms242115819. https://pubmed.ncbi.nlm.nih.gov/37958803/
4. Deng, Yan, Li, Hu, Song, Yi, Chung, Pui Wah Jacqueline, Tang, Tao. 2022. Whole Genome Transcriptomic Analysis of Ovary Granulosa Cells Revealed an Anti-Apoptosis Regulatory Gene DLGAP5 in Polycystic Ovary Syndrome. In Frontiers in endocrinology, 13, 781149. doi:10.3389/fendo.2022.781149. https://pubmed.ncbi.nlm.nih.gov/35370991/
5. Yan, Cheng, Niu, Yandie, Wang, Xuannian. 2022. Blood transcriptome analysis revealed the crosstalk between COVID-19 and HIV. In Frontiers in immunology, 13, 1008653. doi:10.3389/fimmu.2022.1008653. https://pubmed.ncbi.nlm.nih.gov/36389792/
6. Huang, Jie, Zheng, Mengyao, Li, Yan, Xu, Dingwei, Tian, Daguang. 2023. DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP. In Cancer immunology, immunotherapy : CII, 72, 3203-3216. doi:10.1007/s00262-023-03484-6. https://pubmed.ncbi.nlm.nih.gov/37421434/
7. Chen, Ruipu, Liu, Jing, Hu, Jun, Liu, Yanhua, Pan, Weiwei. 2022. DLGAP5 knockdown inactivates the Wnt/β-catenin signal to repress endometrial cancer cell malignant activities. In Environmental toxicology, 38, 685-693. doi:10.1002/tox.23720. https://pubmed.ncbi.nlm.nih.gov/36454672/
8. Tang, Xiaolong, Zhou, Honghong, Liu, Yongshuo. 2023. High Expression of DLGAP5 Indicates Poor Prognosis and Immunotherapy in Lung Adenocarcinoma and Promotes Proliferation through Regulation of the Cell Cycle. In Disease markers, 2023, 9292536. doi:10.1155/2023/9292536. https://pubmed.ncbi.nlm.nih.gov/36712920/
9. Zeng, Xiaoyu, Shi, Gaoli, He, Qiankun, Zhu, Pingping. 2021. Screening and predicted value of potential biomarkers for breast cancer using bioinformatics analysis. In Scientific reports, 11, 20799. doi:10.1038/s41598-021-00268-9. https://pubmed.ncbi.nlm.nih.gov/34675265/
10. Hewit, Kay, Sandilands, Emma, Martinez, Rafael Sanchez, Shanks, Emma, Markert, Elke K. 2018. A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor. In Cell death & disease, 9, 1069. doi:10.1038/s41419-018-1115-7. https://pubmed.ncbi.nlm.nih.gov/30341281/