介导肿瘤细胞G2期周期阻滞的分子机制

doi:10.3760/cma.j.issn.1673422X.2017.03.007

摘要/Abstract

摘要： 肿瘤的形成与进展离不开肿瘤细胞中细胞周期调控蛋白的改变，利用肿瘤细胞的G2M期周期阻滞效应在减缓肿瘤的生长、提高治疗疗效方面尤为重要。DNA损伤的感受器、信号传导因子和效应器是介导肿瘤细胞G2期周期阻滞的经典途径，且有作为新型肿瘤治疗靶点的可能。

关键词: DNA损伤, 细胞周期, 肿瘤

Abstract: The formation and progression of tumor is inseparable from the changes of cell cycle regulatory proteins. The G2M period block effect of tumor cells is especially important in slowing the growth of tumor and improving the curative effect. DNA damage receptor, signal transduction factor and effectors are the classical pathways to mediate G2 phase arrest of tumor cells, and have the potential to be new targets for tumor therapy.

Key words: DNA damage, Cell cycle, Neoplasms

林琳,周菊英. 介导肿瘤细胞G2期周期阻滞的分子机制[J]. 国际肿瘤学杂志, 2017, 44(3): 186-189.

Lin Lin, Zhou Juying. Molecular mechanism of G2 phase cell cycle arrest in tumor cellsLin Lin*, Zhou Juying. *Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou 215000, China[J]. Journal of International Oncology, 2017, 44(3): 186-189.

参考文献

［1］ Meng X, Laidler LL, Kosmacek EA, et al. Induction of mitotic cell death by overriding G2/M checkpoint in endometrial cancer cells with nonfunctional p53［J］. Gynecol Oncol, 2013, 128(3): 461-469. DOI: 10.1016/j.ygyno.2012.11.004. ［2］ Larsen DH, Stucki M. Nucleolar responses to DNA doublestrand breaks ［J］. Nucleic Acids Res, 2016, 44(2): 538544. DOI: 10.1093/nar/gkv1312. ［3］ De Cicco M, Rahim MS, Dames SA. Regulation of the target of rapamycin and other phosphatidylinositol 3kinaserelated kinases by membrane targeting［J］. Membranes, 2015, 5(4): 553-575. DOI: 10.3390/membranes5040553. ［4］ Malaquin N, CarrierLeclerc A, Dessureault M, et al. DDRmediated crosstalk between DNAdamaged cells and their microenvironment［J］. Front Genet, 2015, 6: 94. DOI: 10.3389/fgene.2015.00094. ［5］ Siddiqui MS, Franois M, Fenech MF, et al. Persistent γH2AX: a promising molecular marker of DNA damage and aging［J］. Mutat Res Rev Mutat Res, 2015, 766: 1-19. DOI: 10.1016/j.mrrev.2015.07.001. ［6］ Monsalve DM, CampilloMarcos I, Salzano M, et al. VRK1 phosphorylates and protects NBS1 from ubiquitination and proteasomal degradation in response to DNA damage［J］. Biochim Biophys Acta, 2016, 1863(4): 760-769. DOI: 10.1016/j.bbamcr.2016.02.005. ［7］ Khongkow P, Karunarathna U, Khongkow M, et al. FOXM1 targets NBS1 to regulate DNA damageinduced senescence and epirubicin resistance［J］. Oncogene, 2014, 33(32): 4144-4155. DOI: 10.1038/onc.2013.457. ［8］ Park S, Kang JM, Kim SJ, et al. Smad7 enhances ATM activity by facilitating the interaction between ATM and Mre11Rad50Nbs1 complex in DNA doublestrand break repair［J］. Cell Mol Life Sci, 2015, 72(3): 583- 596. DOI: 10.1007/s000180141687z. ［9］ Liu XY, Zha S. ATMIN: a new tumor suppressor in developing B cells［J ］. Cancer Cell, 2011, 19(5): 569-570. DOI: 10.1016/j.ccr.2011.05.002. ［10］ Loizou JI, Sancho R, Kanu N, et al. ATMIN is required for maintenance of genomic stability and suppression of B cell lymphoma［J］. Cancer Cell, 2011, 19(5): 587-600. DOI: 10.1016/j.ccr.2011.03.022. ［11］ Rizzo A, Salvati E, Porru M, et al. Stabilization of quadruplex DNA perturbs telomere replication leading to the activation of an ATRdependent ATM signaling pathway［J］. Nucleic Acids Res, 2009, 37(16): 5353-5364. DOI: 10.1093/nar/gkp582. ［12］ Spagnolo L, Barbeau J, Curtin NJ, et al. Visualization of a DNAPK/PARP1 complex［J］. Nucleic Acids Res, 2012, 40(9): 4168-4177. DOI: 10.1093/nar/gkr1231. ［13］ VidalEychenie S, Decaillet C, Basbous JA. DNA structurespecific priming of ATR activation by DNAPK［J］. J Cell Biol, 2013, 202(3): 421- 429. DOI: 10.1083/jcb.201304139. ［14］ Xue L, Yu D, Furusawa Y, et al. ATMdependent hyperradiosensitivity in mammalian cells irradiated by heavy ions［J］. Int J Radiat Oncol Biol Phys, 2009, 75(1): 235-243. DOI: 10.1016/j.ijrobp.2009.04.088. ［15］ Cui YX, Palii SS, Innes CL, et al. Depletion of ATR selectively sensitizes ATMdeficient human mammary epithelial cells to ionizing radiation and DNAdamaging agents［J］. Cell Cycle, 2014, 13(22): 3541-3550. DOI: 10.4161/15384101.2014.960729. ［16］ Weber AM, Ryan AJ. ATM and ATR as therapeutic targets in cancer［J］ . Pharmacol Ther, 2015, 149: 124-138. DOI: 10.1016/j.pharmthera.2014.12.001. ［17］ Wang XQ, Redpath JL, Fan ST, et al. ATR dependent activation of Chk2 ［J］. J Cell Physiol, 2006, 208(3): 613-619. DOI: 10.1002/jcp.20700. ［18］ Zhang J, Gao G, Chen L, et al. Hydrogen peroxide/ATRChk2 activation mediates p53 protein stabilization and anticancer activity of cheliensisin a in human cancer cells［J］. Oncotarget, 2014, 5(3): 841-852. ［19］ Niida H, Murata K, Shimada M, et al. Cooperative functions of Chk1 and Chk2 reduce tumour susceptibility in vivo［J］. EMBO J, 2010, 29(20): 3558-3570. DOI: 10.1038/emboj.2010.218. ［20］ Manic G, Obrist F, Sistigu A, et al. Trial watch: targeting ATMCHK2 and ATRCHK1 pathways for anticancer therapy［J］. Mol Cell Oncol, 2015, 2(4): e1012976. DOI: 10.1080/23723556.2015.1012976. ［21］ Lavecchia A, Di Giovanni C, Novellino E. CDC25 phosphatase inhibitors: an update［J］. Mini Rev Med Chem, 2012, 12(1): 62-73. ［22］ Wu YJ, Jan YJ, Ko BS, et al. Involvement of 1433 proteins in regulating tumor progression of hepatocellular carcinoma［J］. Cancers (Basel), 2015, 7(2): 1022-1036. DOI: 10.3390/cancers7020822. ［23］ Agius E, BelVialar S, Bonnet F, et al. Cell cycle and cell fate in the developing nervous system: the role of CDC25B phosphatase［J］. Cell Tissue Res, 2015, 359(1): 201-213. DOI: 10.1007/s0044101419982. ［24］ Vriend LE, De Witt Hamer PC, Van Noorden CJ, et al. WEE1 inhibition and genomic instability in cancer［J］. Biochim Biophys Acta, 2013, 1836 (2): 227-235. DOI: 10.1016/j.bbcan.2013.05.002. ［25］ Li S, Zhang Y, Xu W. Developments of pololike kinase 1 (Plk1) inhibitors as anticancer agents［J］. Mini Rev Med Chem, 2013, 13(14): 2014-2025. ［26］ Wang LM, Lv WW, Zuo D, et al. Characteristics of cyclin B and its potential role in regulating oogenesis in the red claw crayfish (cherax quadricarinatus)［J］. Genet Mol Res, 2015, 14(3): 10786-10798. DOI: 10.4238/2015.September.9.17.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华. Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六. 基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[13]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[14]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[15]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志. 宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.