ERβ 通过使 HIF-1α 不稳定并抑制 VEGF 介导的 snail 核定位来阻碍前列腺癌 EMT：对 Gleason 分级的影响。
ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading.
机构信息
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
出版信息
Cancer Cell. 2010 Apr 13;17(4):319-32. doi: 10.1016/j.ccr.2010.02.030.
Abstract
High Gleason grade prostate carcinomas are aggressive, poorly differentiated tumors that exhibit diminished estrogen receptor beta (ERbeta) expression. We report that a key function of ERbeta and its specific ligand 5alpha-androstane-3beta,17beta-diol (3beta-adiol) is to maintain an epithelial phenotype and repress mesenchymal characteristics in prostate carcinoma. Stimuli (TGF-beta and hypoxia) that induce an epithelial-mesenchymal transition (EMT) diminish ERbeta expression, and loss of ERbeta is sufficient to promote an EMT. The mechanism involves ERbeta-mediated destabilization of HIF-1alpha and transcriptional repression of VEGF-A. The VEGF-A receptor neuropilin-1 drives the EMT by promoting Snail1 nuclear localization. Importantly, this mechanism is manifested in high Gleason grade cancers, which exhibit significantly more HIF-1alpha and VEGF expression, and Snail1 nuclear localization compared to low Gleason grade cancers.
摘要
高分级前列腺癌是侵袭性的、低分化肿瘤，其雌激素受体β（ERβ）表达减少。我们报告 ERβ及其特异性配体 5α-雄烷-3β，17β-二醇（3β-adiol）的一个关键功能是维持前列腺癌中的上皮表型并抑制间充质特征。诱导上皮-间充质转化（EMT）的刺激物（TGF-β和缺氧）会降低 ERβ 的表达，而 ERβ 的缺失足以促进 EMT。该机制涉及 ERβ 介导的 HIF-1α 不稳定性和 VEGF-A 的转录抑制。VEGF-A 受体神经纤毛蛋白-1通过促进 Snail1 核定位来驱动 EMT。重要的是，这种机制在高分级癌症中表现出来，与低分级癌症相比，其表现出显著更高的 HIF-1α 和 VEGF 表达以及 Snail1 核定位。
相似文献
1
ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading.ERβ 通过使 HIF-1α 不稳定并抑制 VEGF 介导的 snail 核定位来阻碍前列腺癌 EMT：对 Gleason 分级的影响。
Cancer Cell. 2010 Apr 13;17(4):319-32. doi: 10.1016/j.ccr.2010.02.030.
2
Estrogen receptor β upregulates FOXO3a and causes induction of apoptosis through PUMA in prostate cancer.雌激素受体β上调FOXO3a并通过PUMA在前列腺癌中诱导细胞凋亡。
Oncogene. 2014 Aug 14;33(33):4213-25. doi: 10.1038/onc.2013.384. Epub 2013 Sep 30.
3
Estrogen receptor β sustains epithelial differentiation by regulating prolyl hydroxylase 2 transcription.雌激素受体β通过调节脯氨酰羟化酶 2 的转录来维持上皮细胞分化。
Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4708-13. doi: 10.1073/pnas.1221654110. Epub 2013 Mar 4.
4
Inhibition of hypoxia inducible factor-1α downregulates the expression of epithelial to mesenchymal transition early marker proteins without undermining cell survival in hypoxic lens epithelial cells.抑制缺氧诱导因子-1α可下调缺氧晶状体上皮细胞中上皮-间质转化早期标志物蛋白的表达，且不影响细胞存活。
Mol Vis. 2015 Sep 1;21:1024-35. eCollection 2015.
5
Estrogen receptor β and 17β-hydroxysteroid dehydrogenase type 6, a growth regulatory pathway that is lost in prostate cancer.雌激素受体β和 17β-羟甾类脱氢酶 6，这是在前列腺癌中丧失的生长调节途径。
Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20090-4. doi: 10.1073/pnas.1117772108. Epub 2011 Nov 23.
6
Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha.缺氧诱导因子-1α诱导的人前列腺癌上皮-间质转化中Wnt/β-连环蛋白信号通路的作用
Int J Urol. 2007 Nov;14(11):1034-9. doi: 10.1111/j.1442-2042.2007.01866.x.
7
ERβ regulation of NF-kB activation in prostate cancer is mediated by HIF-1.雌激素受体β（ERβ）对前列腺癌中核因子κB（NF-κB）激活的调控是由缺氧诱导因子-1（HIF-1）介导的。
Oncotarget. 2015 Nov 24;6(37):40247-54. doi: 10.18632/oncotarget.5377.
8
The epithelial-mesenchymal transition regulators Twist, Slug, and Snail are associated with aggressive tumour features and poor outcome in prostate cancer patients.上皮-间充质转化调节因子 Twist、Slug 和 Snail 与前列腺癌患者侵袭性肿瘤特征和不良预后相关。
J Pathol Clin Res. 2021 May;7(3):253-270. doi: 10.1002/cjp2.202. Epub 2021 Feb 19.
9
Hypoxia-inducible factor-1alpha induces the epithelial-mesenchymal transition of human prostatecancer cells.缺氧诱导因子-1α诱导人前列腺癌细胞的上皮-间质转化。
Chin Med J (Engl). 2006 May 5;119(9):713-8.
10
Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms.缺氧通过缺氧诱导因子和转化生长因子-β依赖的机制刺激肝细胞上皮-间充质转化。
Liver Int. 2010 May;30(5):669-82. doi: 10.1111/j.1478-3231.2010.02205.x. Epub 2010 Feb 15.
引用本文的文献
1
The Role of Heavy Metals in the Biology of Female Cancers.重金属在女性癌症生物学中的作用。
Int J Mol Sci. 2025 May 28;26(11):5155. doi: 10.3390/ijms26115155.
2
Fruquintinib inhibits the migration and invasion of colorectal cancer cells by modulating epithelial-mesenchymal transition via TGF-β/Smad signaling pathway.呋喹替尼通过TGF-β/Smad信号通路调节上皮-间质转化，从而抑制结肠癌细胞的迁移和侵袭。
Front Oncol. 2025 Mar 11;15:1503133. doi: 10.3389/fonc.2025.1503133. eCollection 2025.
3
THSD7A as a novel prognostic factor for colorectal carcinoma.THSD7A作为结直肠癌的一种新的预后因素。
BMC Gastroenterol. 2025 Mar 17;25(1):179. doi: 10.1186/s12876-025-03775-5.
4
Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review).转录因子与激素受体：癌症治疗的性别特异性靶点（综述）
Oncol Lett. 2024 Dec 6;29(2):93. doi: 10.3892/ol.2024.14839. eCollection 2025 Feb.
5
Associations of the Expression Levels and Risk Variants of CDKN2B-AS1 Long Noncoding RNA With the Susceptibility and Progression of Prostate Cancer.CDKN2B-AS1长链非编码RNA的表达水平及风险变异与前列腺癌易感性和进展的关联
J Cell Mol Med. 2024 Dec;28(23):e70264. doi: 10.1111/jcmm.70264.
6
The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors.二甲双胍调控恶性肿瘤代谢重编程的研究进展。
Pharm Res. 2024 Nov;41(11):2143-2159. doi: 10.1007/s11095-024-03783-2. Epub 2024 Oct 25.
7
Genes Co-Expressed with Influence Clinical Outcomes in Cancer Patients: TCGA Data Analysis.与癌症患者临床结局相关的基因共表达分析：TCGA 数据分析。
Int J Mol Sci. 2024 Aug 9;25(16):8707. doi: 10.3390/ijms25168707.
8
Nuclear Estrogen Receptors in Prostate Cancer: From Genes to Function.前列腺癌中的核雌激素受体：从基因到功能
Cancers (Basel). 2023 Sep 20;15(18):4653. doi: 10.3390/cancers15184653.
9
Pharmacological inhibition of KDM1A/LSD1 enhances estrogen receptor beta-mediated tumor suppression in ovarian cancer.KDM1A/LSD1的药理学抑制增强了雌激素受体β介导的卵巢癌肿瘤抑制作用。
Cancer Lett. 2023 Oct 28;575:216383. doi: 10.1016/j.canlet.2023.216383. Epub 2023 Sep 14.
10
Travelling under pressure - hypoxia and shear stress in the metastatic journey.在转移之旅中承受压力 - 缺氧和切变应力。
Clin Exp Metastasis. 2023 Oct;40(5):375-394. doi: 10.1007/s10585-023-10224-8. Epub 2023 Jul 25.
本文引用的文献
1
miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells.miR-200 调节 PDGF-D 介导的前列腺癌细胞上皮-间充质转化、黏附和侵袭。
Stem Cells. 2009 Aug;27(8):1712-21. doi: 10.1002/stem.101.
2
Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion.炎症诱导的细胞迁移和侵袭需要NF-κB对蜗牛蛋白进行稳定作用。
Cancer Cell. 2009 May 5;15(5):416-28. doi: 10.1016/j.ccr.2009.03.016.
3
Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer.内皮型一氧化氮合酶、雌激素受体β和低氧诱导因子在侵袭性人类前列腺癌的预后转录模式激活中协同作用。
J Clin Invest. 2009 May;119(5):1093-108. doi: 10.1172/JCI35079. Epub 2009 Apr 13.
4
Hypoxia-inducible factor 1 alpha activates and is inhibited by unoccupied estrogen receptor beta.缺氧诱导因子1α被未占据的雌激素受体β激活并受到其抑制。
FEBS Lett. 2009 Apr 17;583(8):1314-8. doi: 10.1016/j.febslet.2009.03.028. Epub 2009 Mar 20.
5
Screening and prostate-cancer mortality in a randomized European study.一项欧洲随机研究中的筛查与前列腺癌死亡率
N Engl J Med. 2009 Mar 26;360(13):1320-8. doi: 10.1056/NEJMoa0810084. Epub 2009 Mar 18.
6
Mortality results from a randomized prostate-cancer screening trial.一项前列腺癌随机筛查试验的死亡率结果。
N Engl J Med. 2009 Mar 26;360(13):1310-9. doi: 10.1056/NEJMoa0810696. Epub 2009 Mar 18.
7
Conserved gene expression programs integrate mammalian prostate development and tumorigenesis.保守的基因表达程序整合了哺乳动物前列腺发育和肿瘤发生过程。
Cancer Res. 2009 Mar 1;69(5):1739-47. doi: 10.1158/0008-5472.CAN-07-6817. Epub 2009 Feb 17.
8
Recent trends in gleason grading of prostate cancer. II. Prognosis, reproducibility and reporting.前列腺癌Gleason分级的近期趋势。II. 预后、可重复性及报告
Anal Quant Cytol Histol. 2008 Oct;30(5):254-60.
9
Neuropilin-1 upholds dedifferentiation and propagation phenotypes of renal cell carcinoma cells by activating Akt and sonic hedgehog axes.神经纤毛蛋白-1通过激活Akt和音猬因子信号轴维持肾癌细胞的去分化和增殖表型。
Cancer Res. 2008 Nov 1;68(21):8667-72. doi: 10.1158/0008-5472.CAN-08-2614.
10
Prostate cancer with tertiary Gleason pattern 5 in prostate needle biopsy: clinicopathologic findings and disease progression.前列腺穿刺活检中具有三级Gleason 5级模式的前列腺癌：临床病理特征及疾病进展
Am J Surg Pathol. 2009 Feb;33(2):233-40. doi: 10.1097/PAS.0b013e31817fb3bd.
Zotero 插件