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Guiwen YANG


Guorong LI


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


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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author="Junying GAO, Yan MA, Guiwen YANG, Guorong LI",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T Translationally controlled tumor protein: the mediator promoting cancer invasion and migration and its potential clinical prospects
%A Junying GAO
%A Yan MA
%A Guiwen YANG
%A Guorong LI
%J Journal of Zhejiang University SCIENCE B
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100910

T1 - Translationally controlled tumor protein: the mediator promoting cancer invasion and migration and its potential clinical prospects
A1 - Junying GAO
A1 - Yan MA
A1 - Guiwen YANG
A1 - Guorong LI
J0 - Journal of Zhejiang University Science B
VL - 23
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SP - 642
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%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100910

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.




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[1]AcunzoJ, BaylotV, SoA, et al., 2014. TCTP as therapeutic target in cancers. Cancer Treat Rev, 40(6):760-769.

[2]AlfonsoP, DoladoI, SwatA, et al., 2006. Proteomic analysis of p38α mitogen-activated protein kinase regulated changes in membrane fractions of RAS-transformed fibroblasts. Proteomics, 6(S1):S262-S271.

[3]AmsonR, PeceS, LespagnolA, et al., 2012. Reciprocal repression between P53 and TCTP. Nat Med, 18(1):91-99.

[4]AmsonR, KarpJE, TelermanA, 2013a. Lessons from tumor reversion for cancer treatment. Curr Opin Oncol, 25(1):59-65.

[5]AmsonR, PeceS, MarineJC, et al., 2013b. TPT1/TCTP-regulated pathways in phenotypic reprogramming. Trends Cell Biol, 23(1):37-46.

[6]AmsonR, AuclairC, AndréF, et al., 2017. Targeting TCTP with sertraline and thioridazine in cancer treatment. In: Telerman A, Amson R (Eds.), TCTP/tpt1‍-Remodeling Signaling from Stem Cell to Disease. Springer, Cham, p.283-290.

[7]AmzallagN, PasserBJ, AllanicD, et al., 2004. TSAP6 facilitates the secretion of translationally controlled tumor protein/histamine-releasing factor via a nonclassical pathway. J Biol Chem, 279(44):46104-46112.

[8]ArcuriF, PapaS, CarducciA, et al., 2004. Translationally controlled tumor protein (TCTP) in the human prostate and prostate cancer cells: expression, distribution, and calcium binding activity. Prostate, 60(2):‍130-140.

[9]BaeSY, KimHJ, LeeKJ, et al., 2015. Translationally controlled tumor protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis. Sci Rep, 5:8061.

[10]BaylotV, KatsogiannouM, AndrieuC, et al., 2012. Targeting TCTP as a new therapeutic strategy in castration-resistant prostate cancer. Mol Ther, 20(12):2244-2256.

[11]BaylotV, KarakiS, RocchiP, 2017. TCTP has a crucial role in the different stages of prostate cancer malignant progression. In: Telerman A, Amson R (Eds.), TCTP/tpt1-Remodeling Signaling from Stem Cell to Disease. Springer, Cham, p.255-261.

[12]BazileF, PascalA, ArnalI, et al., 2009. Complex relationship between TCTP, microtubules and actin microfilaments regulates cell shape in normal and cancer cells. Carcinogenesis, 30(4):555-565.

[13]BellNJ, HuntRH, 1992. Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease. Gut, 33(1):118-124.

[14]BommerUA, ThieleBJ, 2004. The translationally controlled tumour protein (TCTP). Int J Biochem Cell Biol, 36(3):379-385.

[15]BonhoureA, VallentinA, MartinM, et al., 2017. Acetylation of translationally controlled tumor protein promotes its degradation through chaperone-mediated autophagy. Eur J Cell Biol, 96(2):83-98.

[16]BrioudesF, ThierryAM, ChambrierP, et al., 2010. Translationally controlled tumor protein is a conserved mitotic growth integrator in animals and plants. Proc Natl Acad Sci USA, 107(37):16384-16389.

[17]CansC, PasserBJ, ShalakV, et al., 2003. Translationally controlled tumor protein acts as a guanine nucleotide dissociation inhibitor on the translation elongation factor eEF1A. Proc Natl Acad Sci USA, 100(24):‍13892-13897.

[18]ChafferCL, WeinbergRA, 2011. A perspective on cancer cell metastasis. Science, 331(6024):1559-1564.

[19]ChanTHM, ChenLL, GuanXY, 2012a. Role of translationally controlled tumor protein in cancer progression. Biochem Res Int, 2012:369384.

[20]ChanTHM, ChenLL, LiuM, et al., 2012b. Translationally controlled tumor protein induces mitotic defects and chromosome missegregation in hepatocellular carcinoma development. Hepatology, 55(2):491-505.

[21]ChenC, DengY, HuaMH, et al., 2015. Expression and clinical role of TCTP in epithelial ovarian cancer. J Mol Histol, 46(2):145-156.

[22]ChenYL, YanMY, ChienSY, et al., 2013. Sann-Joong-Kuey-Jian-Tang inhibits hepatocellular carcinoma Hep-G2 cell proliferation by increasing TNF-‍α, Caspase-8, Caspase-3 and Bax but by decreasing TCTP and Mcl-1 expression in vitro. Mol Med Rep, 7(5):1487-1493.

[23]ChengCY, LinYH, SuCC, 2010. Curcumin inhibits the proliferation of human hepatocellular carcinoma J5 cells by inducing endoplasmic reticulum stress and mitochondrial dysfunction. Int J Mol Med, 26(5):673-678.

[24]ChinnapakaS, BAkthavachalamV, MunirathinamG, 2020. Repurposing antidepressant sertraline as a pharmacological drug to target prostate cancer stem cells: dual activation of apoptosis and autophagy signaling by deregulating redox balance. Am J Cancer Res, 10(7):2043-2065.

[25]ChoJH, ParkS, KimS, et al., 2022. RKIP induction promotes tumor differentiation via SOX2 degradation in NF2-deficient conditions. Mol Cancer Res, 20(3):412-424.

[26]ChoiS, MinHJ, KimM, et al., 2009. Proton pump inhibitors exert anti-allergic effects by reducing TCTP secretion. PLoS ONE, 4(6):e5732.

[27]ChuZH, LiuL, ZhengCX, et al., 2011. Proteomic analysis identifies translationally controlled tumor protein as a mediator of phosphatase of regenerating liver-3-promoted proliferation, migration and invasion in human colon cancer cells. Chin Med J, 124(22):3778-3785.

[28]D'AmicoS, KrasnowskaEK, ManniI, et al., 2020. DHA affects microtubule dynamics through reduction of phospho-TCTP levels and enhances the antiproliferative effect of T-DM1 in trastuzumab-resistant HER2-positive breast cancer cell lines. Cells, 9(5):1260.

[29]DongXC, YangB, LiYJ, et al., 2009. Molecular basis of the acceleration of the GDP-GTP exchange of human Ras homolog enriched in brain by human translationally controlled tumor protein. J Biol Chem, 284(35):23754-23764.

[30]FischerN, SeoEJ, KlingerA, et al., 2021. AMG900 as novel inhibitor of the translationally controlled tumor protein. Chem Biol Interact, 334:109349.

[31]FujitaT, FelixK, PinkaewD, et al., 2008. Human fortilin is a molecular target of dihydroartemisinin. FEBS Lett, 582(7):1055-1060.

[32]GaoJY, MaFJ, WangXJ, et al., 2020. Combination of dihydroartemisinin and resveratrol effectively inhibits cancer cell migration via regulation of the DLC1/TCTP/Cdc42 pathway. Food Funct, 11(11):9573-9584.

[33]GrossB, GaestelM, BöhmH, et al., 1989. cDNA sequence coding for a translationally controlled human tumor protein. Nucleic Acids Res, 17(20):8367.

[34]HaghighatNG, RubenL, 1992. Purification of novel calcium binding proteins from Trypanosoma brucei: properties of 22-, 24- and 38-kilodalton proteins. Mol Biochem Parasitol, 51(1):99-110.

[35]HoKW, LambertWS, CalkinsDJ, 2014. Activation of the TRPV1 cation channel contributes to stress-induced astrocyte migration. GLIA, 62(9):1435-1451.

[36]HoweAK, 2004. Regulation of actin-based cell migration by cAMP/PKA. Biochim Biophys Acta (BBA)‍-Mol Cell Res, 1692(2-3):159-174.

[37]HsuYC, ChernJJ, CaiY, et al., 2007. Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase. Nature, 445(7129):785-788.

[38]HuangCY, ChiuTL, KuoSJ, et al., 2013. Tanshinone IIA inhibits the growth of pancreatic cancer BxPC-3 cells by decreasing protein expression of TCTP, MCL-1 and Bcl-xL. Mol Med Rep, 7(3):1045-1049.

[39]HuangHY, LiX, HuGH, et al., 2015. Poly(ADP-ribose) glycohydrolase silencing down-regulates TCTP and Cofilin-1 associated with metastasis in benzo(a)pyrene carcinogenesis. Am J Cancer Res, 5(1):155-167.

[40]HuangM, GengY, DengQ, et al., 2018. Translationally controlled tumor protein affects colorectal cancer metastasis through the high mobility group box 1-dependent pathway. Int J Oncol, 53(4):1481-1492.

[41]IshidaH, JensenKV, WoodmanAG, et al., 2017. The calcium-dependent switch helix of l-plastin regulates actin bundling. Sci Rep, 7:40662.

[42]JaglarzMK, BazileF, LaskowskaK, et al., 2012. Association of TCTP with centrosome and microtubules. Biochem Res Int, 2012:541906.

[43]JinH, ZhangXX, SuJ, et al., 2015. RNA interference-mediated knockdown of translationally controlled tumor protein induces apoptosis, and inhibits growth and invasion in glioma cells. Mol Med Rep, 12(5):6617-6625.

[44]KimM, JungY, LeeK, et al., 2000. Identification of the calcium binding sites in translationally controlled tumor protein. Arch Pharm Res, 23(6):633-636.

[45]KlocM, TejpalN, SidhuJ, et al., 2012. Inverse relationship between TCTP/RhoA and p53/cyclin A/actin expression in ovarian cancer cells. Folia Histochem Cytobiol, 50(3):358-367.

[46]KoziolMJ, GurdonJB, 2012. TCTP in development and cancer. Biochem Res Int, 2012:105203.

[47]LeeJS, JangEH, WooHA, et al., 2020. Regulation of autophagy is a novel tumorigenesis-related activity of multifunctional translationally controlled tumor protein. Cells, 9(1):257.

[48]LiF, ZhangD, FujiseK, 2001. Characterization of fortilin, a novel antiapoptotic protein. J Biol Chem, 276(50):47542-47549.

[49]LiuLZ, WangMH, XinQH, et al., 2020. The permissive role of TCTP in PM2.5/NNK-induced epithelial-mesenchymal transition in lung cells. J Transl Med, 18:66.

[50]LiuTY, ZhouLL, XiaoY, et al., 2022. BRAF inhibitors reprogram cancer-associated fibroblasts to drive matrix remodeling and therapeutic escape in melanoma. Cancer Res, 82(3):419-432.

[51]LowtherWT, WeissbachH, EtienneF, et al., 2002. The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB. Nat Struct Biol, 9(5):348-352.

[52]LucibelloM, AdantiS, AntelmiE, et al., 2015. Phospho-TCTP as a therapeutic target of Dihydroartemisinin for aggressive breast cancer cells. Oncotarget, 6(7):‍5275-5291.

[53]LupasAN, ZhuHB, KorycinskiM, 2015. The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the β‍-tent fold. PLoS Comput Biol, 11(1):e1004023.

[54]MaQ, GengY, XuWW, et al., 2010. The role of translationally controlled tumor protein in tumor growth and metastasis of colon adenocarcinoma cells. J Proteome Res, 9(1):40-49.

[55]MacDonaldSM, RafnarT, LangdonJ, et al., 1995. Molecular identification of an IgE-dependent histamine-releasing factor. Science, 269(5224):688-690.

[56]MertensAE, RooversRC, CollardJG, 2003. Regulation of Tiam1-Rac signalling. FEBS Lett, 546(1):11-16.

[57]MishraDK, SrivastavaP, SharmaA, et al., 2018. Translationally controlled tumor protein (TCTP) is required for TGF-‍β1 induced epithelial to mesenchymal transition and influences cytoskeletal reorganization. Biochim Biophys Acta (BBA)‍-‍Mol Cell Res, 1865(1):67-75.

[58]Nagano-ItoM, IchikawaS, 2012. Biological effects of mammalian translationally controlled tumor protein (TCTP) on cell death, proliferation, and tumorigenesis. Biochem Res Int, 2012:204960.

[59]PacherP, KecskemetiV, 2004. Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns? Curr Pharm Des, 10(20):2463-2475.

[60]PhanthapholN, TechasenA, LoilomeW, et al., 2017. Upregulation of TCTP is associated with cholangiocarcinoma progression and metastasis. Oncol Lett, 14(5):5973-5979.

[61]ProiettiS, CucinaA, PensottiA, et al., 2019. Active fraction from embryo fish extracts induces reversion of the malignant invasive phenotype in breast cancer through down-regulation of TCTP and modulation of E-cadherin/β-catenin pathway. Int J Mol Sci, 20(9):2151.

[62]RaghavamenonAC, MuyiwaAF, DavisLK, et al., 2011. Dihydroartemisinin induces caspase-8-dependent apoptosis in murine GT1-7 hypothalamic neurons. Toxicol Mech Methods, 21(5):367-373.

[63]RamaniP, NashR, Sowa-AvugrahE, et al., 2015. High levels of polo-like kinase 1 and phosphorylated translationally controlled tumor protein indicate poor prognosis in neuroblastomas. J Neurooncol, 125(1):103-111.

[64]RehmannH, BrüningM, BerghausC, et al., 2008. Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb. FEBS Lett, 582(20):3005-3010.

[65]RenJB, MaoXX, ChenMH, et al., 2015. TCTP expression after rat spinal cord injury: implications for astrocyte proliferation and migration. J Mol Neurosci, 57(3):‍366-375.

[66]RhoSB, LeeJH, ParkMS, et al., 2011. Anti-apoptotic protein TCTP controls the stability of the tumor suppressor p53. FEBS Lett, 585(1):29-35.

[67]SeoEJ, EfferthT, 2016. Interaction of antihistaminic drugs with human translationally controlled tumor protein (TCTP) as novel approach for differentiation therapy. Oncotarget, 7(13):16818-16839.

[68]SuCC, 2014. Tanshinone IIA inhibits human gastric carcinoma AGS cell growth by decreasing BiP, TCTP, Mcl-1 and Bcl-xL and increasing Bax and CHOP protein expression. Int J Mol Med, 34(6):‍1661-1668.

[69]SunRL, LuX, GongL, et al., 2019. TCTP promotes epithelial-mesenchymal transition in lung adenocarcinoma. OncoTargets Ther, 12:1641-1653.

[70]SusiniL, BesseS, DuflautD, et al., 2008. TCTP protects from apoptotic cell death by antagonizing Bax function. Cell Death Differ, 15(8):‍1211-1220.

[71]ThawP, BaxterNJ, HounslowAM, et al., 2001. Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones. Nat Struct Biol, 8(8):‍701-704.

[72]TsarovaK, YarmolaEG, BubbMR, 2010. Identification of a cofilin-like actin-binding site on translationally controlled tumor protein (TCTP). FEBS Lett, 584(23):4756-4760.

[73]TuynderM, SusiniL, PrieurS, et al., 2002. Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1. Proc Natl Acad Sci USA, 99(23):14976-14981.

[74]TuynderM, FiucciG, PrieurS, et al., 2004. Translationally controlled tumor protein is a target of tumor reversion. Proc Natl Acad Sci USA, 101(43):15364-15369.

[75]van RheenenJ, CondeelisJ, GlogauerM, 2009. A common cofilin activity cycle in invasive tumor cells and inflammatory cells. J Cell Sci, 122(3):305-311.

[76]WandallJH, 1992. Effects of omeprazole on neutrophil chemotaxis, super oxide production, degranulation, and translocation of cytochrome b-245. Gut, 33(5):617-621.

[77]WangLL, TangYF, ZhaoMJ, et al., 2018. Knockdown of translationally controlled tumor protein inhibits growth, migration and invasion of lung cancer cells. Life Sci, 193:292-299.

[78]WangXM, FonsecaBD, TangH, et al., 2008. Re-evaluating the roles of proposed modulators of mammalian target of rapamycin complex 1 (mTORC1) signaling. J Biol Chem, 283(45):30482-30492.

[79]WangZX, WangZ, LiGH, et al., 2017. CXCL1 from tumor-associated lymphatic endothelial cells drives gastric cancer cell into lymphatic system via activating integrin β1/FAK/AKT signaling. Cancer Lett, 385:28-38.

[80]WeiY, RedelC, AhlnerA, et al., 2022. The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase. Nucleic Acids Res, 50(6):‍3505-3522.

[81]XiaoB, ChenDX, LuoSH, et al., 2016. Extracellular translationally controlled tumor protein promotes colorectal cancer invasion and metastasis through Cdc42/JNK/MMP9 signaling. Oncotarget, 7(31):50057-50073.

[82]YaoY, JiaXY, TianHY, et al., 2009. Comparative proteomic analysis of colon cancer cells in response to oxaliplatin treatment. Biochim Biophys Acta (BBA)‍-‍Proteins Proteom, 1794(10):1433-1440.

[83]YarmFR, 2002. Plk phosphorylation regulates the microtubule-stabilizing protein TCTP. Mol Cell Biol, 22(17):‍6209-6221.

[84]YuQL, ZhangB, ZhangYM, et al., 2020. Actin cytoskeleton-disrupting and magnetic field-responsive multivalent supramolecular assemblies for efficient cancer therapy. ACS Appl Mater Interfaces, 12(12):13709-13717.

[85]ZhangF, LiuB, WangZ, et al., 2013. A novel regulatory mechanism of Pim-3 kinase stability and its involvement in pancreatic cancer progression. Mol Cancer Res, 11(12):1508-1520.

[86]ZhangF, MaQ, XuZH, et al., 2017. Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer. J Exp Clin Cancer Res, 36:68.

[87]ZhouC, FanZS, ZhouZH, et al., 2022. Discovery of the first-in-class agonist-based SOS1 PROTACs effective in human cancer cells harboring various KRAS mutations. J Med Chem, 65(5):3923-3942.

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