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 eleven β-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.
摘要：
翻译控制的肿瘤蛋白（TCTP）是一种高度保守的多功能蛋白，位于真核细胞的细胞质和细胞核中。它通过外泌体分泌，其降解与泛素-蛋白酶体系统（UPS）有关，热休克蛋白27（Hsp27），和伴侣介导的自噬（CMA）。它的结构包含三个α-螺旋和十一条β-链，并以螺旋形发夹为标志。TCTP与Sec4（Mss4/Dss4）蛋白家族的甲硫氨酸-R-亚砜还原酶B（MsrB）和哺乳动物抑制因子具有显着的相似性，对小鸟苷三磷酸酶（GTPase）蛋白发挥鸟嘌呤核苷酸交换因子（GEF）活性，这表明TCTP的某些功能可能至少取决于其全球环境基金的行动。的确,TCTP对脑中富集的Ras同系物(Rheb)发挥GEF活性,以促进果蝇细胞的生长和增殖。TCTP还增强细胞分裂控制蛋白42同源物（Cdc42）的表达，以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）蛋白相互作用并诱导上皮-间质转化（EMT）过程来调节细胞骨架组织。实质上,TCTP促进癌细胞运动。它通常在癌组织中高表达，从而降低患者生存率;同时，药物可以靶向TCTP来减少这种影响。在这次审查中,我们总结了TCTP促进肿瘤侵袭和迁移的机制,并描述了目前在癌症疾病中靶向TCTP的抑制策略。
