肿瘤发生中的关键 DNA 损伤途径。
Critical DNA damaging pathways in tumorigenesis.
机构信息
Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA; Mayo Clinic Medical Scientist Training Program, Mayo Clinic, Rochester, MN, 55905, USA.
Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
出版信息
Semin Cancer Biol. 2022 Oct;85:164-184. doi: 10.1016/j.semcancer.2021.04.012. Epub 2021 Apr 24.
Abstract
The acquisition of DNA damage is an early driving event in tumorigenesis. Premalignant lesions show activated DNA damage responses and inactivation of DNA damage checkpoints promotes malignant transformation. However, DNA damage is also a targetable vulnerability in cancer cells. This requires a detailed understanding of the cellular and molecular mechanisms governing DNA integrity. Here, we review current work on DNA damage in tumorigenesis. We discuss DNA double strand break repair, how repair pathways contribute to tumorigenesis, and how double strand breaks are linked to the tumor microenvironment. Next, we discuss the role of oncogenes in promoting DNA damage through replication stress. Finally, we discuss our current understanding on DNA damage in micronuclei and discuss therapies targeting these DNA damage pathways.
摘要
DNA 损伤的获得是肿瘤发生的早期驱动事件。癌前病变显示出激活的 DNA 损伤反应，而 DNA 损伤检查点的失活则促进恶性转化。然而，DNA 损伤也是癌细胞中可靶向的弱点。这需要对维持 DNA 完整性的细胞和分子机制有详细的了解。在这里，我们综述了肿瘤发生过程中 DNA 损伤的最新研究进展。我们讨论了 DNA 双链断裂修复，修复途径如何促进肿瘤发生，以及双链断裂如何与肿瘤微环境相关联。接下来，我们讨论了致癌基因在通过复制应激促进 DNA 损伤方面的作用。最后，我们讨论了我们目前对微核中 DNA 损伤的理解，并讨论了针对这些 DNA 损伤途径的治疗方法。
相似文献
1
Critical DNA damaging pathways in tumorigenesis.肿瘤发生中的关键 DNA 损伤途径。
Semin Cancer Biol. 2022 Oct;85:164-184. doi: 10.1016/j.semcancer.2021.04.012. Epub 2021 Apr 24.
2
Protein ADP-ribosylation and the cellular response to DNA strand breaks.蛋白质 ADP 核糖基化与细胞对 DNA 链断裂的反应。
DNA Repair (Amst). 2014 Jul;19:108-13. doi: 10.1016/j.dnarep.2014.03.021. Epub 2014 Apr 20.
3
Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis.Rnf8 和 p53 协同作用保护基因组不稳定性和肿瘤发生。
PLoS Genet. 2013;9(1):e1003259. doi: 10.1371/journal.pgen.1003259. Epub 2013 Jan 31.
4
DNA replication stress and cancer: cause or cure?DNA复制应激与癌症：病因还是疗法？
Future Oncol. 2016 Jan;12(2):221-37. doi: 10.2217/fon.15.292. Epub 2015 Nov 30.
5
MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress.MRE11通过促进对癌基因诱导的复制应激的抗性来促进肿瘤发生。
Cancer Res. 2017 Oct 1;77(19):5327-5338. doi: 10.1158/0008-5472.CAN-17-1355. Epub 2017 Aug 17.
6
Interplay between the cell cycle and double-strand break response in mammalian cells.哺乳动物细胞中细胞周期与双链断裂反应之间的相互作用。
Methods Mol Biol. 2014;1170:41-59. doi: 10.1007/978-1-4939-0888-2_3.
7
Processing DNA lesions during mitosis to prevent genomic instability.在有丝分裂过程中处理 DNA 损伤，以防止基因组不稳定。
Biochem Soc Trans. 2022 Aug 31;50(4):1105-1118. doi: 10.1042/BST20220049.
8
DNA repair gene--XRCC1 in relation to genome instability and role in colorectal carcinogenesis.DNA 修复基因 XRCC1 与基因组不稳定性及结直肠癌发生中的作用。
Oncol Res Treat. 2014;37(7-8):418-22. doi: 10.1159/000364898. Epub 2014 Jun 17.
9
DNA double-strand break repair pathway choice and cancer.DNA双链断裂修复途径的选择与癌症
DNA Repair (Amst). 2014 Jul;19:169-75. doi: 10.1016/j.dnarep.2014.03.014. Epub 2014 Apr 18.
10
Regulatory and Functional Involvement of Long Non-Coding RNAs in DNA Double-Strand Break Repair Mechanisms.长链非编码 RNA 在 DNA 双链断裂修复机制中的调控和功能作用。
Cells. 2021 Jun 15;10(6):1506. doi: 10.3390/cells10061506.
引用本文的文献
1
Environmental Hazards and Glial Brain Tumors: Association or Causation?环境危害与胶质脑肿瘤：关联还是因果关系？
Int J Mol Sci. 2025 Aug 1;26(15):7425. doi: 10.3390/ijms26157425.
2
Phosphorylation of USP32 by CDK5 regulates Rap1 stability and therapeutic resistance in pancreatic ductal adenocarcinoma.CDK5介导的USP32磷酸化调控胰腺导管腺癌中Rap1的稳定性及治疗抗性
Oncogene. 2025 May 16. doi: 10.1038/s41388-024-03263-2.
3
TOX High-Mobility Group Box Family Member 4 promotes DNA double-strand break repair via nonhomologous end joining.TOX高迁移率族盒蛋白家族成员4通过非同源末端连接促进DNA双链断裂修复。
J Biol Chem. 2025 May 4;301(6):110174. doi: 10.1016/j.jbc.2025.110174.
4
The association between breast cancer and lung cancer: a bidirectional Mendelian randomization study.乳腺癌与肺癌的相关性：一项双向孟德尔随机化研究。
Sci Rep. 2024 Nov 6;14(1):26942. doi: 10.1038/s41598-024-76314-z.
5
Metal nanoparticles for cancer therapy: Precision targeting of DNA damage.用于癌症治疗的金属纳米颗粒：DNA损伤的精准靶向
Acta Pharm Sin B. 2024 Mar;14(3):1132-1149. doi: 10.1016/j.apsb.2023.08.031. Epub 2023 Sep 3.
6
CDK1 promotes the phosphorylation of KIFC1 to regulate the tumorgenicity of endometrial carcinoma.CDK1 促进 KIFC1 的磷酸化来调节子宫内膜癌的致瘤性。
J Gynecol Oncol. 2024 Sep;35(5):e68. doi: 10.3802/jgo.2024.35.e68. Epub 2024 Feb 26.
7
SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair.SMYD3通过对非同源末端连接修复中LIG4/XRCC4/XLF复合物的表观遗传调控促进子宫内膜癌。
Oncogenesis. 2024 Jan 8;13(1):3. doi: 10.1038/s41389-023-00503-0.
8
TRAIP suppressed apoptosis and cell cycle to promote prostate cancer proliferation via TRAF2-PI3K-AKT pathway activation.TRAIP 通过 TRAF2-PI3K-AKT 通路的激活抑制细胞凋亡和细胞周期来促进前列腺癌的增殖。
Int Urol Nephrol. 2024 May;56(5):1639-1648. doi: 10.1007/s11255-023-03890-w. Epub 2023 Dec 15.
9
Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies.衰老、氧化应激与退行性疾病：机制、并发症与新兴治疗策略。
Biogerontology. 2023 Oct;24(5):609-662. doi: 10.1007/s10522-023-10050-1. Epub 2023 Jul 30.
10
SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity.SMYD2 抑制介导的 Ku70 低甲基化导致非同源末端连接修复受损和抗肿瘤免疫抑制。
Sci Adv. 2023 Jun 16;9(24):eade6624. doi: 10.1126/sciadv.ade6624. Epub 2023 Jun 14.
本文引用的文献
1
Super-sonic speed of DNA synthesis in medulloblastoma.髓母细胞瘤中DNA合成的超高速率
Nat Cancer. 2020 Aug;1(8):758-760. doi: 10.1038/s43018-020-0105-8.
2
Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma.音猬因子加速DNA复制，引发复制应激，促进髓母细胞瘤的癌症起始。
Nat Cancer. 2020 Aug;1(8):840-854. doi: 10.1038/s43018-020-0094-7. Epub 2020 Jul 20.
3
Extracellular cGAMP is a cancer cell-produced immunotransmitter involved in radiation-induced anti-cancer immunity.细胞外 cGAMP 是一种癌细胞产生的免疫递质，参与放射诱导的抗肿瘤免疫。
Nat Cancer. 2020 Feb;1(2):184-196. doi: 10.1038/s43018-020-0028-4. Epub 2020 Feb 24.
4
Exploiting synthetic lethality to target BRCA1/2-deficient tumors: where we stand.利用合成致死性靶向 BRCA1/2 缺陷型肿瘤：现状。
Oncogene. 2021 Apr;40(17):3001-3014. doi: 10.1038/s41388-021-01744-2. Epub 2021 Mar 14.
5
Inhibition of ATM Induces Hypersensitivity to Proton Irradiation by Upregulating Toxic End Joining.抑制 ATM 可通过上调毒性末端连接诱导对质子照射的超敏反应。
Cancer Res. 2021 Jun 15;81(12):3333-3346. doi: 10.1158/0008-5472.CAN-20-2960. Epub 2021 Feb 17.
6
Phosphorylation and chromatin tethering prevent cGAS activation during mitosis.磷酸化和染色质连接防止有丝分裂过程中环鸟苷酸-腺苷酸合成酶（cGAS）的激活。
Science. 2021 Mar 19;371(6535). doi: 10.1126/science.abc5386. Epub 2021 Feb 4.
7
ER-directed TREX1 limits cGAS activation at micronuclei.内质网定向的 TREX1 限制微核中环鸟苷酸-腺苷酸合成酶的激活。
Mol Cell. 2021 Feb 18;81(4):724-738.e9. doi: 10.1016/j.molcel.2020.12.037. Epub 2021 Jan 20.
8
Tracking break-induced replication shows that it stalls at roadblocks.追踪断裂诱导复制表明，它在路障处停滞。
Nature. 2021 Feb;590(7847):655-659. doi: 10.1038/s41586-020-03172-w. Epub 2021 Jan 20.
9
ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells.ALC1 将染色质可及性与同源重组缺陷细胞中 PARP 抑制剂的反应联系起来。
Nat Cell Biol. 2021 Feb;23(2):160-171. doi: 10.1038/s41556-020-00624-3. Epub 2021 Jan 18.
10
The Rad51 paralog complex Rad55-Rad57 acts as a molecular chaperone during homologous recombination.Rad51 同源物复合物 Rad55-Rad57 在同源重组过程中充当分子伴侣。
Mol Cell. 2021 Mar 4;81(5):1043-1057.e8. doi: 10.1016/j.molcel.2020.12.019. Epub 2021 Jan 8.
Zotero 插件