• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

GPR44 的激活通过特异性靶向白血病起始干细胞降低髓性白血病的严重程度。

Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells.

机构信息

Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.

Department of Medicine, Division of Hematology and Oncology, Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

出版信息

Cell Rep. 2023 Jul 25;42(7):112794. doi: 10.1016/j.celrep.2023.112794. Epub 2023 Jul 18.

DOI:10.1016/j.celrep.2023.112794
PMID:37459233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10428076/
Abstract

Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ-PGJ, and 15d-PGJ, which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic analysis of GPR44 LICs indicated that GPR44 activation by CyPGs suppressed KRAS-mediated MAPK and PI3K/AKT/mTOR signaling pathways, to enhance apoptosis. Our studies show the role of GPR44, providing mechanistic underpinnings of the chemopreventive and chemotherapeutic properties of selenium and CyPGs in AML.

摘要

急性髓系白血病（AML）的复发仍然是一个重大问题，因为大多数现有疗法通常无法针对持续存在的白血病起始干细胞（LICs）。我们使用小鼠 AML 模型、人 AML 细胞系和患者样本表明，AML LICs 对内源性和外源性环戊烯酮前列腺素 J（CyPG）、Δ-PGJ 和 15d-PGJ 敏感，这些物质在通过环加氧酶-造血 PGD 合酶途径补充膳食硒时会增加。CyPGs 是过氧化物酶体增殖物激活受体 γ 和 GPR44（CRTH2；PTGDR2）的内源性配体。在 AML 的小鼠模型中敲除 GPR44 会加重疾病，表明 GPR44 的激活介导了硒介导的 LICs 凋亡。对 GPR44 LICs 的转录组分析表明，CyPG 激活 GPR44 会抑制 KRAS 介导的 MAPK 和 PI3K/AKT/mTOR 信号通路，从而增强细胞凋亡。我们的研究表明了 GPR44 的作用，为硒和 CyPGs 在 AML 中的化学预防和化学治疗特性提供了机制基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/de368d4b5a47/nihms-1920514-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/c30764744a11/nihms-1920514-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/39465ff435ac/nihms-1920514-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/a09b70c0df24/nihms-1920514-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/703179da598e/nihms-1920514-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/3a9c391b4c62/nihms-1920514-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/10e894ede1a7/nihms-1920514-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/de368d4b5a47/nihms-1920514-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/c30764744a11/nihms-1920514-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/39465ff435ac/nihms-1920514-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/a09b70c0df24/nihms-1920514-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/703179da598e/nihms-1920514-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/3a9c391b4c62/nihms-1920514-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/10e894ede1a7/nihms-1920514-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19fc/10428076/de368d4b5a47/nihms-1920514-f0008.jpg

相似文献

1
Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells.GPR44 的激活通过特异性靶向白血病起始干细胞降低髓性白血病的严重程度。
Cell Rep. 2023 Jul 25;42(7):112794. doi: 10.1016/j.celrep.2023.112794. Epub 2023 Jul 18.
2
Activation of PPARγ by endogenous prostaglandin J mediates the antileukemic effect of selenium in murine leukemia.内源性前列腺素J对PPARγ的激活介导了硒在小鼠白血病中的抗白血病作用。
Blood. 2017 Mar 30;129(13):1802-1810. doi: 10.1182/blood-2016-08-736405. Epub 2017 Jan 23.
3
Interleukin-4 treatment reduces leukemia burden in acute myeloid leukemia.白细胞介素-4 治疗可降低急性髓系白血病的白血病负担。
FASEB J. 2022 May;36(5):e22328. doi: 10.1096/fj.202200251R.
4
Crth2 receptor signaling down-regulates lipopolysaccharide-induced NF-κB activation in murine macrophages changes in intracellular calcium.Crth2 受体信号转导下调脂多糖诱导的 NF-κB 在小鼠巨噬细胞中的激活 细胞内钙离子的变化。
FASEB J. 2019 Nov;33(11):12838-12852. doi: 10.1096/fj.201802608R. Epub 2019 Sep 13.
5
Selenoprotein-dependent up-regulation of hematopoietic prostaglandin D2 synthase in macrophages is mediated through the activation of peroxisome proliferator-activated receptor (PPAR) gamma.硒蛋白依赖性上调巨噬细胞中造血前列腺素 D2 合酶是通过过氧化物酶体增殖物激活受体 (PPAR)γ的激活来介导的。
J Biol Chem. 2011 Aug 5;286(31):27471-82. doi: 10.1074/jbc.M111.260547. Epub 2011 Jun 13.
6
Intra-heterogeneity in transcription and chemoresistant property of leukemia-initiating cells in murine Setd2 acute myeloid leukemia.鼠 Setd2 急性髓系白血病中白血病起始细胞转录和化疗耐药性的异质性。
Cancer Commun (Lond). 2021 Sep;41(9):867-888. doi: 10.1002/cac2.12189. Epub 2021 Jul 1.
7
A combination of temsirolimus, an allosteric mTOR inhibitor, with clofarabine as a new therapeutic option for patients with acute myeloid leukemia.替西罗莫司（一种变构mTOR抑制剂）与氯法拉滨联合使用，作为急性髓系白血病患者的一种新治疗选择。
Oncotarget. 2012 Dec;3(12):1615-28. doi: 10.18632/oncotarget.762.
8
Rheb1 promotes tumor progression through mTORC1 in MLL-AF9-initiated murine acute myeloid leukemia.Rheb1通过mTORC1促进MLL - AF9引发的小鼠急性髓性白血病的肿瘤进展。
J Hematol Oncol. 2016 Apr 12;9:36. doi: 10.1186/s13045-016-0264-3.
9
Targeting mTOR signaling pathways and related negative feedback loops for the treatment of acute myeloid leukemia.靶向mTOR信号通路及相关负反馈环治疗急性髓系白血病。
Cancer Biol Ther. 2015;16(5):648-56. doi: 10.1080/15384047.2015.1026510.
10
New insights into Notch1 regulation of the PI3K-AKT-mTOR1 signaling axis: targeted therapy of γ-secretase inhibitor resistant T-cell acute lymphoblastic leukemia.深入了解 Notch1 对 PI3K-AKT-mTOR1 信号轴的调控：γ-分泌酶抑制剂耐药 T 细胞急性淋巴细胞白血病的靶向治疗。
Cell Signal. 2014 Jan;26(1):149-61. doi: 10.1016/j.cellsig.2013.09.021. Epub 2013 Oct 16.

引用本文的文献

1
Selenium compounds for cancer prevention and therapy - human clinical trial considerations.用于癌症预防和治疗的硒化合物——人体临床试验考量
Med Rev (2021). 2025 Jan 6;5(3):203-230. doi: 10.1515/mr-2024-0065. eCollection 2025 Jun.
2
PGD2/PTGDR2 signaling pathway affects the self-renewal capacity of gastric cancer stem cells by regulating ATG4B ubiquitination.PGD2/PTGDR2信号通路通过调节自噬相关蛋白4B（ATG4B）的泛素化来影响胃癌干细胞的自我更新能力。
Front Oncol. 2024 Dec 24;14:1496050. doi: 10.3389/fonc.2024.1496050. eCollection 2024.
3
Advances in PGD2/PTGDR2 signaling pathway in tumors: A review.

本文引用的文献

1
Interleukin-4 treatment reduces leukemia burden in acute myeloid leukemia.白细胞介素-4 治疗可降低急性髓系白血病的白血病负担。
FASEB J. 2022 May;36(5):e22328. doi: 10.1096/fj.202200251R.
2
An oncogenic enhancer encodes selective selenium dependency in AML.一种致癌增强子编码急性髓系白血病中的选择性硒依赖性。
Cell Stem Cell. 2022 Apr 7;29(4):650. doi: 10.1016/j.stem.2022.03.006.
3
High PGD receptor 2 levels are associated with poor prognosis in colorectal cancer patients and induce VEGF expression in colon cancer cells and migration in a zebrafish xenograft model.
肿瘤中 PGD2/PTGDR2 信号通路的研究进展：综述。
Biomol Biomed. 2024 Sep 6;24(5):1055-1067. doi: 10.17305/bb.2024.10485.
高 PGD 受体 2 水平与结直肠癌患者预后不良相关，并在结直肠癌细胞中诱导 VEGF 表达和斑马鱼异种移植模型中的迁移。
Br J Cancer. 2022 Mar;126(4):586-597. doi: 10.1038/s41416-021-01595-4. Epub 2021 Nov 8.
4
Lentiviral-Driven Discovery of Cancer Drug Resistance Mutations.慢病毒驱动的癌症药物耐药突变发现。
Cancer Res. 2021 Sep 15;81(18):4685-4695. doi: 10.1158/0008-5472.CAN-21-1153. Epub 2021 Jul 23.
5
Oxidative Stress and ROS-Mediated Signaling in Leukemia: Novel Promising Perspectives to Eradicate Chemoresistant Cells in Myeloid Leukemia.氧化应激与 ROS 介导的信号通路在白血病中的作用：一种根除髓系白血病中耐药细胞的新的有前途的策略。
Int J Mol Sci. 2021 Feb 28;22(5):2470. doi: 10.3390/ijms22052470.
6
Compartmentalized GPCR Signaling from Intracellular Membranes.细胞内膜区室化的 G 蛋白偶联受体信号转导
J Membr Biol. 2021 Jun;254(3):259-271. doi: 10.1007/s00232-020-00158-7. Epub 2020 Nov 24.
7
Mesenchymal PGD activates an ILC2-Treg axis to promote proliferation of normal and malignant HSPCs.间充质 PGD 通过激活 ILC2-Treg 轴促进正常和恶性 HSPC 的增殖。
Leukemia. 2020 Nov;34(11):3028-3041. doi: 10.1038/s41375-020-0843-8. Epub 2020 May 4.
8
Synthetic miR-143 Exhibited an Anti-Cancer Effect via the Downregulation of K-RAS Networks of Renal Cell Cancer Cells In Vitro and In Vivo.合成 miR-143 通过下调肾癌细胞中的 K-RAS 网络在体外和体内发挥抗癌作用。
Mol Ther. 2019 May 8;27(5):1017-1027. doi: 10.1016/j.ymthe.2019.03.004. Epub 2019 Mar 13.
9
PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer.PGD2/PTGDR2 信号限制胃癌的自我更新和肿瘤发生。
Stem Cells. 2018 Jul;36(7):990-1003. doi: 10.1002/stem.2821. Epub 2018 Apr 4.
10
Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.肿瘤来源的前列腺素D2（PGD2）与自然杀伤细胞蛋白30（NKp30）-B7同源物6（B7H6）相互作用驱动免疫抑制性2型固有淋巴细胞（ILC2）-骨髓来源的抑制性细胞（MDSC）轴。
Nat Commun. 2017 Sep 19;8(1):593. doi: 10.1038/s41467-017-00678-2.