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

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.

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

Fig. 1. TCTP promotes the EMT process by downregulating epithelial markers and upregulating mesenchymal markers. TCTP: translationally controlled tumor protein; EMT: epithelial-mesenchymal transition; α‍‍-SMA: α‍-smooth muscle actin.

Fig. 2. Underlying oncogenic mechanisms of TCTP during cancer cell invasion and migration. TCTP associates with MTs and MFs and interacts with these proteins, leading to cell proliferation, invasion, and metastasis, and this function of TCTP can be inhibited by drugs. Cdc42: cell division control protein 42 homolog; ECM: extracellular matrix; FAK: focal adhesion kinase; F-actin: filamentous actin; G-actin: globular actin; MF: microfilament; MMPs: matrix metallopeptidases; MRCK: myotonic dystrophy kinase-related Cdc42-binding kinase; MT: microtubule; mTORC1: mammalian target of rapamycin complex 1; N-WASP: neural Wiskott-Aldrich syndrome protein; Pak: p21-activated kinase; Rheb: Ras homolog enriched in brain; TCTP: translationally controlled tumor protein.