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

期刊

JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
卷 23, 期 8, 页码 642-654

出版社

ZHEJIANG UNIV PRESS
DOI: 10.1631/jzus.B2100910

关键词

Translationally controlled tumor protein (TCTP); Invasion; Migration; Cancer; Clinical drugs

资金

  1. National Natural Science Foundation of China [31672377]

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The translated paragraph provides a comprehensive overview of the highly conserved multifunctional protein, Translationally controlled tumor protein (TCTP), and its role in promoting cancer invasion and migration. It also highlights the current inhibitory strategies targeting TCTP in cancerous diseases.
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 alpha-helices and eleven beta-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.

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