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On-line Access: 2022-08-12

Received: 2021-11-02

Revision Accepted: 2022-04-01

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Guiwen YANG

https://orcid.org/0000-0002-0957-6730

Guorong LI

https://orcid.org/0000-0002-9439-4754

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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.8 P.642-654

http://doi.org/10.1631/jzus.B2100910


Translationally controlled tumor protein: the mediator promoting cancer invasion and migration and its potential clinical prospects


Author(s):  Junying GAO, Yan MA, Guiwen YANG, Guorong LI

Affiliation(s):  Shandong Provincial Key Laboratory of Animal Resistant, School of Life Sciences, Shandong Normal University, Jinan 250014, China

Corresponding email(s):   yanggw@sdnu.edu.cn, grli@sdnu.edu.cn

Key Words:  Translationally controlled tumor protein (TCTP), Invasion, Migration, Cancer, Clinical drugs


Junying GAO, Yan MA, Guiwen YANG, Guorong LI. Translationally controlled tumor protein: the mediator promoting cancer invasion and migration and its potential clinical prospects[J]. Journal of Zhejiang University Science B, 2022, 23(8): 642-654.

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Abstract: 
translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associated with the ubiquitin-proteasome system (UPS), heat shock protein 27 (Hsp27), and chaperone-mediated autophagy (CMA). Its structure contains three α‍-helices and elevenβ‍-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B (MsrB) and mammalian suppressor of Sec4 (Mss4/Dss4) protein families, which exerts guanine nucleotide exchange factor (GEF) activity on small guanosine triphosphatase (GTPase) proteins, suggesting that some functions of TCTP may at least depend on its GEF action. Indeed, TCTP exerts GEF activity on Ras homolog enriched in brain (Rheb) to boost the growth and proliferation of Drosophila cells. TCTP also enhances the expression of cell division control protein 42 homolog (Cdc42) to promote cancer cell invasion and migration. Moreover, TCTP regulates cytoskeleton organization by interacting with actin microfilament (MF) and microtubule (MT) proteins and inducing the epithelial-mesenchymal transition (EMT) process. In essence, TCTP promotes cancer cell movement. It is usually highly expressed in cancerous tissues and thus reduces patient survival; meanwhile, drugs can target TCTP to reduce this effect. In this review, we summarize the mechanisms of TCTP in promoting cancer invasion and migration, and describe the current inhibitory strategy to target TCTP in cancerous diseases.

翻译控制肿瘤蛋白促进癌症侵袭和迁移及其潜在的临床前景

高俊英,马妍,杨桂文,李国荣
山东师范大学生命科学学院,山东省动物抗性重点实验室,中国济南市,250014
概要:翻译控制肿瘤蛋白(TCTP)定位于真核细胞的细胞质和细胞核,是一种高度保守的多功能蛋白。它以外泌体的方式分泌,通过泛素-蛋白酶体系统(UPS)、热休克蛋白27(Hsp27)和分子伴侣介导的自噬(CMA)发生降解。TCTP的结构包含3个α-螺旋和11个β-链,并以螺旋发夹作为其结构特征。TCTP与蛋氨酸-R-亚砜还原酶B(MsrB)和哺乳动物Sec4抑制蛋白家族(Mss4/Dss4)的结构有很强的相似性,这些蛋白家族对小分子GTPase发挥鸟嘌呤核苷酸交换因子(GEF)的活性,表明TCTP的某些功能可能依赖于GEF的活性。TCTP对Rheb发挥GEF活性以促进果蝇细胞的生长和增殖。TCTP增强细胞分裂控制蛋白42(Cdc42)的表达从而促进癌细胞的侵袭和迁移。此外,TCTP通过与肌动蛋白微丝(MF)和微管(MT)蛋白结合来调控细胞骨架重排,并参与诱导上皮-间充质转化(EMT)的过程。因此,TCTP促进癌细胞运动。TCTP在癌组织中通常高表达,这减少了患者的存活率,然而药物能靶向TCTP会降低其促癌作用。本文综述了TCTP促进癌细胞侵袭和迁移的机制,并介绍了目前在癌症中抑制TCTP的策略。

关键词:翻译控制肿瘤蛋白(TCTP);侵袭;迁移;癌症;临床药物

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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