整合素通过调节p53来调控对DNA损伤的凋亡反应。
Integrins regulate the apoptotic response to DNA damage through modulation of p53.
作者信息
Lewis Jean McArthur, Truong Tony Nguyen, Schwartz Martin Alexander
机构信息
Department of Vascular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CVN228/VB4, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3627-32. doi: 10.1073/pnas.062698499.
Abstract
p53 mediates apoptosis of cells after DNA damage including tumor cells after radiation or chemotherapy. Survival of isolated cancer cells after therapy leads to recurrence of therapy-resistant tumors. We now show that for some melanoma, sarcoma, or fibroblastic cell types that survive without integrin-mediated adhesion, apoptosis in response to DNA damage requires cell adhesion. This effect correlates with rapid changes in levels of p14/p19 Arf and its downstream component, p53. Killing of nonadherent cells is increased by treatment with antiintegrin antibodies or by increasing levels of p53 or Arf. Consistent with low p53 levels, suspended cells show chromosomal instability after irradiation. Thus, loss of normal adhesion in susceptible tumor cells during genotoxic stress may play a role in therapy resistance and promote survival of cells with aberrant DNA.
摘要
p53介导DNA损伤后细胞的凋亡，包括放疗或化疗后的肿瘤细胞。治疗后分离的癌细胞存活会导致抗治疗性肿瘤复发。我们现在表明，对于一些在没有整合素介导的黏附情况下仍能存活的黑色素瘤、肉瘤或成纤维细胞类型，DNA损伤后的凋亡需要细胞黏附。这种效应与p14/p19 Arf及其下游成分p53水平的快速变化相关。用抗整合素抗体治疗或提高p53或Arf水平可增加对非黏附细胞的杀伤。与低p53水平一致，悬浮细胞在照射后表现出染色体不稳定。因此，在基因毒性应激期间，易感肿瘤细胞正常黏附的丧失可能在治疗抗性中起作用，并促进DNA异常细胞的存活。
相似文献
1
Integrins regulate the apoptotic response to DNA damage through modulation of p53.整合素通过调节p53来调控对DNA损伤的凋亡反应。
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3627-32. doi: 10.1073/pnas.062698499.
2
p14ARF is a component of the p53 response following ionizing irradiation of normal human fibroblasts.p14ARF是正常人成纤维细胞受到电离辐射后p53反应的一个组成部分。
Oncogene. 2004 Aug 12;23(36):6040-6. doi: 10.1038/sj.onc.1207824.
3
Mdm2 regulates p53 independently of p19(ARF) in homeostatic tissues.在稳态组织中，Mdm2独立于p19(ARF)对p53进行调控。
Mol Cell Biol. 2004 Jan;24(1):186-91. doi: 10.1128/MCB.24.1.186-191.2004.
4
p19(ARF) is dispensable for oncogenic stress-induced p53-mediated apoptosis and tumor suppression in vivo.p19（ARF）在体内致癌应激诱导的p53介导的细胞凋亡和肿瘤抑制过程中并非必需。
Mol Cell Biol. 2002 Jan;22(1):370-7. doi: 10.1128/MCB.22.1.370-377.2002.
5
p53-independent apoptosis is induced by the p19ARF tumor suppressor.p19ARF肿瘤抑制因子可诱导不依赖p53的细胞凋亡。
Biochem Biophys Res Commun. 2002 Jul 19;295(3):621-9. doi: 10.1016/s0006-291x(02)00723-4.
6
Deregulation of the TP53/p14ARF tumor suppressor pathway in low-grade diffuse astrocytomas and its influence on clinical course.低级别弥漫性星形细胞瘤中TP53/p14ARF肿瘤抑制通路的失调及其对临床病程的影响。
Clin Cancer Res. 2003 Oct 15;9(13):4884-90.
7
P16(INK4A) is implicated in both the immediate and adaptative response of human keratinocytes to UVB irradiation.P16（INK4A）在人类角质形成细胞对紫外线B照射的即时反应和适应性反应中均有涉及。
Oncogene. 2002 Apr 18;21(17):2652-61. doi: 10.1038/sj.onc.1205349.
8
Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization.细胞应激和DNA损伤引发了时间上不同的Mdm2、p53和PML复合物以及损伤特异性的核重新定位。
J Cell Sci. 2003 Oct 1;116(Pt 19):3917-25. doi: 10.1242/jcs.00714. Epub 2003 Aug 12.
9
Systematic genetic dissection of p14ARF-mediated mitochondrial cell death signaling reveals a key role for p21CDKN1 and the BH3-only protein Puma/bbc3.系统遗传剖析 p14ARF 介导的线粒体细胞死亡信号转导揭示了 p21CDKN1 和 BH3 仅蛋白 Puma/bbc3 的关键作用。
J Mol Med (Berl). 2010 Jun;88(6):609-22. doi: 10.1007/s00109-010-0606-5. Epub 2010 Apr 25.
10
Oncomir miR-125b suppresses p14(ARF) to modulate p53-dependent and p53-independent apoptosis in prostate cancer.抑癌 miR-125b 通过调控 p14(ARF) 抑制前列腺癌细胞凋亡。
PLoS One. 2013 Apr 9;8(4):e61064. doi: 10.1371/journal.pone.0061064. Print 2013.
引用本文的文献
1
Electrospun Polymer Fiber Mats for Persulfide Prodrug Delivery.用于过硫化物前药递送的电纺聚合物纤维垫
Biomacromolecules. 2025 Sep 8;26(9):6057-6069. doi: 10.1021/acs.biomac.5c00975. Epub 2025 Aug 1.
2
Cell confluency affects p53 dynamics in response to DNA damage.细胞汇合度会影响p53对DNA损伤的反应动力学。
Mol Biol Cell. 2025 Jun 1;36(6):br16. doi: 10.1091/mbc.E24-09-0394. Epub 2025 Apr 9.
3
Single-cell and bulk transcriptional profiling of mouse ovaries reveals novel genes and pathways associated with DNA damage response in oocytes.小鼠卵巢的单细胞和整体转录谱分析揭示了与卵母细胞DNA损伤反应相关的新基因和途径。
Dev Biol. 2025 Jan;517:55-72. doi: 10.1016/j.ydbio.2024.09.007. Epub 2024 Sep 19.
4
Single-cell and bulk transcriptional profiling of mouse ovaries reveals novel genes and pathways associated with DNA damage response in oocytes.小鼠卵巢的单细胞和整体转录谱分析揭示了与卵母细胞DNA损伤反应相关的新基因和信号通路。
bioRxiv. 2024 Feb 4:2024.02.02.578648. doi: 10.1101/2024.02.02.578648.
5
Effects of Scaffolds on Urine- and Urothelial Carcinoma Tissue-Derived Organoids from Bladder Cancer Patients.支架对膀胱癌患者尿液和尿路上皮癌组织衍生类器官的影响。
Cells. 2023 Aug 20;12(16):2108. doi: 10.3390/cells12162108.
6
p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.p53 在多柔比星诱导的心脏毒性和耐药性之间的十字路口：营养平衡的作用。
Nutrients. 2023 May 10;15(10):2259. doi: 10.3390/nu15102259.
7
Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer.α6β4整合素和网蛋白对前列腺癌激酶信号通路的调控
Cancers (Basel). 2022 Dec 27;15(1):149. doi: 10.3390/cancers15010149.
8
A Novel Glycolysis-Related Long Noncoding RNA Signature for Predicting Overall Survival in Gastric Cancer.一种新型与糖酵解相关的长非编码 RNA 标志物用于预测胃癌患者的总生存期。
Pathol Oncol Res. 2022 Nov 7;28:1610643. doi: 10.3389/pore.2022.1610643. eCollection 2022.
9
Differential biological responses of adherent and non-adherent (cancer and non-cancerous) cells to variable extremely low frequency magnetic fields.贴壁和非贴壁（癌和非癌）细胞对可变极低频磁场的差异生物学反应。
Sci Rep. 2022 Aug 20;12(1):14225. doi: 10.1038/s41598-022-18210-y.
10
Roles of reactive oxygen species, mitochondrial membrane potential, and p53 in evodiamine-induced apoptosis and G2/M arrest of human anaplastic thyroid carcinoma cells.活性氧、线粒体膜电位和p53在吴茱萸碱诱导人未分化甲状腺癌细胞凋亡及G2/M期阻滞中的作用
Chin Med. 2021 Dec 9;16(1):134. doi: 10.1186/s13020-021-00505-3.
本文引用的文献
1
A novel host cell reactivation assay to assess homologous recombination capacity in human cancer cell lines.一种用于评估人类癌细胞系中同源重组能力的新型宿主细胞复活试验。
Biochem Biophys Res Commun. 2001 Feb 16;281(1):212-9. doi: 10.1006/bbrc.2001.4335.
2
Regulation of cell death by the Abl tyrosine kinase.Abl酪氨酸激酶对细胞死亡的调控
Oncogene. 2000 Nov 20;19(49):5643-50. doi: 10.1038/sj.onc.1203878.
3
p53: death star.p53：死亡之星。
Cell. 2000 Nov 22;103(5):691-4. doi: 10.1016/s0092-8674(00)00171-9.
4
Opposing effects of Ras on p53: transcriptional activation of mdm2 and induction of p19ARF.Ras对p53的相反作用：mdm2的转录激活和p19ARF的诱导。
Cell. 2000 Oct 13;103(2):321-30. doi: 10.1016/s0092-8674(00)00123-9.
5
p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53.p53AIP1，一种p53依赖性凋亡的潜在介质，以及其受Ser-46磷酸化p53的调控。
Cell. 2000 Sep 15;102(6):849-62. doi: 10.1016/s0092-8674(00)00073-8.
6
p53-independent functions of the p19(ARF) tumor suppressor.p19(ARF)肿瘤抑制因子的p53非依赖性功能。
Genes Dev. 2000 Sep 15;14(18):2358-65. doi: 10.1101/gad.827300.
7
Requirement of wild-type p53 protein for maintenance of chromosomal integrity.维持染色体完整性对野生型p53蛋白的需求。
Mol Carcinog. 2000 Aug;28(4):203-14. doi: 10.1002/1098-2744(200008)28:4<203::aid-mc3>3.0.co;2-1.
8
Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization.整合素介导的生存信号通过其构象和亚细胞定位调节Bax的凋亡功能。
J Cell Biol. 2000 Apr 17;149(2):431-46. doi: 10.1083/jcb.149.2.431.
9
DNA damage-induced activation of p53 by the checkpoint kinase Chk2.由关卡激酶Chk2介导的DNA损伤诱导的p53激活。
Science. 2000 Mar 10;287(5459):1824-7. doi: 10.1126/science.287.5459.1824.
10
DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes.DNA双链断裂修复蛋白是封闭哺乳动物染色体末端所必需的。
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14899-904. doi: 10.1073/pnas.96.26.14899.
Zotero 插件