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作 者:Junying GAO Yan MA Guiwen YANG Guorong LI
出 处:《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2022年第8期642-654,共13页浙江大学学报(英文版)B辑(生物医学与生物技术)
基 金:funded by the National Natural Science Foundation of China(No.31672377)。
摘 要: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 eleven β-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B(Msr B) 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.
关 键 词:Translationally controlled tumor protein(TCTP) INVASION MIGRATION Cancer Clinical drugs
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