Wnt 拮抗剂 SFRP1 作为衰老的分泌介质发挥作用。
Wnt antagonist SFRP1 functions as a secreted mediator of senescence.
机构信息
Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA.
出版信息
Mol Cell Biol. 2012 Nov;32(21):4388-99. doi: 10.1128/MCB.06023-11. Epub 2012 Aug 27.
Abstract
Cellular senescence has emerged as a critical tumor suppressive mechanism in recent years, but relatively little is known about how senescence occurs. Here, we report that secreted Frizzled-related protein 1 (SFRP1), a secreted antagonist of Wnt signaling, is oversecreted upon cellular senescence caused by DNA damage or oxidative stress. SFRP1 is necessary for stress-induced senescence caused by these factors and is sufficient for the induction of senescence phenotypes. We present evidence suggesting that SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma (Rb) pathway and that cancer-associated SFRP1 mutants are defective for senescence induction.
摘要
近年来，细胞衰老已成为一种重要的肿瘤抑制机制，但人们对衰老的发生机制知之甚少。在这里，我们报告称，分泌型卷曲相关蛋白 1（SFRP1）是 Wnt 信号的一种分泌型拮抗剂，在由 DNA 损伤或氧化应激引起的细胞衰老过程中会过度分泌。SFRP1 是这些因素引起的应激诱导衰老所必需的，并且足以诱导衰老表型。我们提供的证据表明，SFRP1 通过抑制 Wnt 信号和激活视网膜母细胞瘤（Rb）途径来作为衰老的分泌介质发挥作用，并且与癌症相关的 SFRP1 突变体不能诱导衰老。
相似文献
1
Wnt antagonist SFRP1 functions as a secreted mediator of senescence.Wnt 拮抗剂 SFRP1 作为衰老的分泌介质发挥作用。
Mol Cell Biol. 2012 Nov;32(21):4388-99. doi: 10.1128/MCB.06023-11. Epub 2012 Aug 27.
2
Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells.与年龄相关的Wnt抑制剂增加会导致人类心脏干细胞出现衰老样表型。
Biochem Biophys Res Commun. 2017 Jun 3;487(3):653-659. doi: 10.1016/j.bbrc.2017.04.110. Epub 2017 Apr 21.
3
Functional analyses and prognostic significance of SFRP1 expression in bladder cancer.SFRP1在膀胱癌中的功能分析及预后意义
J Cancer Res Clin Oncol. 2015 Oct;141(10):1779-90. doi: 10.1007/s00432-015-1942-1. Epub 2015 Mar 4.
4
Epigenetic inactivation of the canonical Wnt antagonist secreted frizzled-related protein 1 in hepatocellular carcinoma cells.肝细胞癌中经典 Wnt 拮抗剂分泌型卷曲相关蛋白 1 的表观遗传失活。
Neoplasma. 2012;59(3):326-32. doi: 10.4149/neo_2012_042.
5
In vivo and in vitro effects of microRNA-27a on proliferation, migration and invasion of breast cancer cells through targeting of SFRP1 gene via Wnt/β-catenin signaling pathway.微小RNA-27a通过Wnt/β-连环蛋白信号通路靶向SFRP1基因对乳腺癌细胞增殖、迁移和侵袭的体内外作用
Oncotarget. 2017 Feb 28;8(9):15507-15519. doi: 10.18632/oncotarget.14662.
6
Change in gene expression profiles of secreted frizzled-related proteins (SFRPs) by sodium butyrate in gastric cancers: induction of promoter demethylation and histone modification causing inhibition of Wnt signaling.丁酸钠对胃癌中分泌型卷曲相关蛋白（SFRP）基因表达谱的影响：诱导启动子去甲基化和组蛋白修饰，从而抑制 Wnt 信号通路。
Int J Oncol. 2012 May;40(5):1533-42. doi: 10.3892/ijo.2012.1327. Epub 2012 Jan 10.
7
WNT antagonist, SFRP1, is Hedgehog signaling target.WNT拮抗剂SFRP1是刺猬信号通路的靶点。
Int J Mol Med. 2006 Jan;17(1):171-5.
8
9
Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma.Wnt信号通路的阻断抑制肝细胞癌中的血管生成和肿瘤生长。
Cancer Res. 2009 Sep 1;69(17):6951-9. doi: 10.1158/0008-5472.CAN-09-0541. Epub 2009 Aug 18.
10
WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth.WNT 信号通路增强乳腺癌细胞的迁移能力，而 sFRP1 阻断 WNT 通路则可抑制 MDA-MB-231 异种移植瘤的生长。
Breast Cancer Res. 2009;11(3):R32. doi: 10.1186/bcr2317. Epub 2009 May 27.
引用本文的文献
1
Substrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts.底物硬度决定了人肺成纤维细胞中独特的阿霉素诱导的衰老相关分泌表型和转录组特征。
Geroscience. 2025 Jan 18. doi: 10.1007/s11357-025-01507-x.
2
β-Asarone Inhibits Carboplatin Resistance in Retinoblastoma Cells Through the UCA1/miR-206/NRP1 Axis.β-细辛醚通过UCA1/miR-206/NRP1轴抑制视网膜母细胞瘤细胞中的卡铂耐药性。
Biochem Genet. 2024 Dec 24. doi: 10.1007/s10528-024-10985-1.
3
Substrate Stiffness Dictates Unique Doxorubicin-induced Senescence-associated Secretory Phenotypes and Transcriptomic Signatures in Human Pulmonary Fibroblasts.底物硬度决定了阿霉素诱导的人肺成纤维细胞中独特的衰老相关分泌表型和转录组特征。
bioRxiv. 2024 Nov 21:2024.11.18.623471. doi: 10.1101/2024.11.18.623471.
4
Wnt16 Promotes Vascular Smooth Muscle Contractile Phenotype and Function via Taz (Wwtr1) Activation in Male LDLR-/- Mice.Wnt16 通过激活 Taz（Wwtr1）促进雄性 LDLR-/- 小鼠血管平滑肌收缩表型和功能。
Endocrinology. 2023 Dec 23;165(2). doi: 10.1210/endocr/bqad192.
5
MiRNA-related metastasis in oral cancer: moving and shaking.口腔癌中与微小RNA相关的转移：动态变化
Cancer Cell Int. 2023 Aug 27;23(1):182. doi: 10.1186/s12935-023-03022-5.
6
Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development.幽门螺杆菌激活的成纤维细胞作为胃癌发展中的沉默伙伴。
Cancer Metastasis Rev. 2023 Dec;42(4):1219-1256. doi: 10.1007/s10555-023-10122-1. Epub 2023 Jul 17.
7
Deconstructing heterogeneity of replicative senescence in human mesenchymal stem cells at single cell resolution.单细胞分辨率解析人骨髓间充质干细胞复制性衰老的异质性。
Geroscience. 2024 Feb;46(1):999-1015. doi: 10.1007/s11357-023-00829-y. Epub 2023 Jun 14.
8
A senescence-based prognostic gene signature for colorectal cancer and identification of the role of SPP1-positive macrophages in tumor senescence.基于衰老的结直肠癌预后基因特征，并鉴定 SPP1 阳性巨噬细胞在肿瘤衰老中的作用。
Front Immunol. 2023 Apr 6;14:1175490. doi: 10.3389/fimmu.2023.1175490. eCollection 2023.
9
Slit2 signaling stimulates Ewing sarcoma growth.Slit2信号传导刺激尤因肉瘤生长。
Genes Cancer. 2022 Dec 14;13:88-99. doi: 10.18632/genesandcancer.227. eCollection 2022.
10
TRIM36 inhibits tumorigenesis through the Wnt/β-catenin pathway and promotes caspase-dependent apoptosis in hepatocellular carcinoma.TRIM36通过Wnt/β-连环蛋白通路抑制肿瘤发生，并促进肝细胞癌中依赖半胱天冬酶的凋亡。
Cancer Cell Int. 2022 Sep 6;22(1):278. doi: 10.1186/s12935-022-02692-x.
本文引用的文献
1
An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.一种将肽的串联质谱数据与蛋白质数据库中氨基酸序列相关联的方法。
J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89. doi: 10.1016/1044-0305(94)80016-2.
2
Spatial coupling of mTOR and autophagy augments secretory phenotypes.mTOR 和自噬的空间偶联增强了分泌表型。
Science. 2011 May 20;332(6032):966-70. doi: 10.1126/science.1205407. Epub 2011 Apr 21.
3
Quantitative proteomics identifies the Myb-binding protein p160 as a novel target of the von Hippel-Lindau tumor suppressor.定量蛋白质组学鉴定 Myb 结合蛋白 p160 为 von Hippel-Lindau 肿瘤抑制因子的一个新靶标。
PLoS One. 2011 Feb 28;6(2):e16975. doi: 10.1371/journal.pone.0016975.
4
Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes.Wnt 信号通路需要将糖原合酶激酶 3（GSK3）隔离在多泡内体（MVEs）中。
Cell. 2010 Dec 23;143(7):1136-48. doi: 10.1016/j.cell.2010.11.034.
5
The essence of senescence.衰老的本质。
Genes Dev. 2010 Nov 15;24(22):2463-79. doi: 10.1101/gad.1971610.
6
Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α.通过激活酪蛋白激酶 1α抑制 Wnt 信号通路的小分子。
Nat Chem Biol. 2010 Nov;6(11):829-36. doi: 10.1038/nchembio.453. Epub 2010 Oct 3.
7
Wnt signaling regulates mitochondrial physiology and insulin sensitivity.Wnt 信号通路调控线粒体生理学和胰岛素敏感性。
Genes Dev. 2010 Jul 15;24(14):1507-18. doi: 10.1101/gad.1924910.
8
The senescence-associated secretory phenotype: the dark side of tumor suppression.衰老相关的分泌表型：肿瘤抑制的阴暗面。
Annu Rev Pathol. 2010;5:99-118. doi: 10.1146/annurev-pathol-121808-102144.
9
Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network.细胞表面结合的 IL-1alpha 是衰老相关的 IL-6/IL-8 细胞因子网络的上游调节剂。
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17031-6. doi: 10.1073/pnas.0905299106. Epub 2009 Sep 28.
10
Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling.端锚聚合酶抑制可使轴蛋白稳定并拮抗Wnt信号通路。
Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16.
Zotero 插件