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TCTP 通过细胞间囊泡信号调节遗传毒性应激和致瘤性。

TCTP regulates genotoxic stress and tumorigenicity via intercellular vesicular signaling.

机构信息

Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France.

Université de Paris Cité & CNRS, Expression Génétique Microbienne, IBPC, 13 rue Pierre et Marie Curie and Institut de Biologie Physico-Chimique, Paris Sciences et Lettres University, CNRS UMR8261, EGM, 75005, Paris, France.

出版信息

EMBO Rep. 2024 Apr;25(4):1962-1986. doi: 10.1038/s44319-024-00108-7. Epub 2024 Mar 28.

DOI:10.1038/s44319-024-00108-7
PMID:38548973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11014985/
Abstract

Oncogenic intercellular signaling is regulated by extracellular vesicles (EVs), but the underlying mechanisms remain mostly unclear. Since TCTP (translationally controlled tumor protein) is an EV component, we investigated whether it has a role in genotoxic stress signaling and malignant transformation. By generating a Tctp-inducible knockout mouse model (Tctp), we report that Tctp is required for genotoxic stress-induced apoptosis signaling via small EVs (sEVs). Human breast cancer cells knocked-down for TCTP show impaired spontaneous EV secretion, thereby reducing sEV-dependent malignant growth. Since Trp53 mice are prone to tumor formation, we derived tumor cells from Trp53;Tctp double mutant mice and describe a drastic decrease in tumori-genicity with concomitant decrease in sEV secretion and content. Remarkably, Trp53;Tctp mice show highly prolonged survival. Treatment of Trp53 mice with sertraline, which inhibits TCTP function, increases their survival. Mechanistically, TCTP binds DDX3, recruiting RNAs, including miRNAs, to sEVs. Our findings establish TCTP as an essential protagonist in the regulation of sEV-signaling in the context of apoptosis and tumorigenicity.

摘要

致癌细胞间信号受细胞外囊泡 (EVs) 调控，但其中的潜在机制仍大多不清楚。由于 TCTP（翻译控制肿瘤蛋白）是 EV 的组成部分，我们研究了它是否在遗传毒性应激信号和恶性转化中发挥作用。通过生成 Tctp 诱导型敲除小鼠模型 (Tctp)，我们报告 Tctp 通过小细胞外囊泡 (sEVs) 参与遗传毒性应激诱导的细胞凋亡信号。敲低 TCTP 的人乳腺癌细胞显示自发 EV 分泌受损，从而减少 sEV 依赖性恶性生长。由于 Trp53 小鼠易发生肿瘤形成，我们从 Trp53;Tctp 双突变小鼠中获得肿瘤细胞，并描述了 sEV 分泌和含量减少导致的致瘤性急剧下降。值得注意的是，Trp53;Tctp 小鼠的存活时间显著延长。用抑制 TCTP 功能的舍曲林治疗 Trp53 小鼠可增加其存活时间。从机制上讲，TCTP 与 DDX3 结合，将包括 miRNAs 在内的 RNA 募集到 sEVs 中。我们的研究结果确立了 TCTP 在凋亡和致瘤性背景下调节 sEV 信号中的重要作用。

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2
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Nat Plants. 2021 Mar;7(3):342-352. doi: 10.1038/s41477-021-00863-8. Epub 2021 Feb 25.
3
DDX3X: structure, physiologic functions and cancer.
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Mol Cancer. 2021 Feb 24;20(1):38. doi: 10.1186/s12943-021-01325-7.
4
Isolation and characterization of extracellular vesicle subpopulations from tissues.从组织中分离和表征细胞外囊泡亚群。
Nat Protoc. 2021 Mar;16(3):1548-1580. doi: 10.1038/s41596-020-00466-1. Epub 2021 Jan 25.
5
A novel ligand of the translationally controlled tumor protein (TCTP) identified by virtual drug screening for cancer differentiation therapy.一种通过虚拟药物筛选鉴定的肿瘤蛋白翻译控制因子（TCTP）新型配体可用于癌症分化治疗。
Invest New Drugs. 2021 Aug;39(4):914-927. doi: 10.1007/s10637-020-01042-w. Epub 2021 Jan 25.
6
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7
Dysregulation of TCTP in Biological Processes and Diseases.TCTP 在生物过程和疾病中的失调。
Cells. 2020 Jul 7;9(7):1632. doi: 10.3390/cells9071632.
8
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10
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