Roles and mechanisms of β-thymosins in cell migration and cancer metastasis: An update

Cancer Investigation

Volumn 31, Issue 2, 2013, Pages 103-110

  Sribenja, Sirinapa ^a,b   Wongkham, Sopit ^b   Wongkham, Chaisiri ^b   Yao, Qizhi ^a   Chen, Changyi ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b KHON KAEN UNIVERSITY   (Thailand)

Author keywords

Thymosins; Actin sequestering; Cancer Metastasis; Epithelial to mesenchymal Transition; Migration; Thymosin 10; Thymosin 4

Indexed keywords

BETA ACTIN; BETA THYMOSIN; THYMOSIN; UNCLASSIFIED DRUG;

ANGIOGENESIS; ARTICLE; BILE DUCT CARCINOMA; BLADDER CANCER; BREAST CANCER; CELL ACTIVITY; CELL DIFFERENTIATION; CELL FATE; CELL FUNCTION; CELL MIGRATION; CENTRAL NERVOUS SYSTEM; ENDOTHELIUM CELL; EPITHELIUM CELL; ESOPHAGUS CANCER; HEART DEVELOPMENT; HUMAN; LUNG CANCER; MELANOMA; METASTASIS; NERVE REGENERATION; NEUROBLASTOMA; NONHUMAN; OVARY TUMOR; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN ASSEMBLY; STOMACH CANCER; THYROID CARCINOMA; UTERINE CERVIX CANCER;

ACTINS; ANIMALS; CELL MOVEMENT; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; NEOPLASM METASTASIS; NEOPLASMS; THYMOSIN;

EID: 84873131613     PISSN: 07357907     EISSN: 15324192     Source Type: Journal    
DOI: 10.3109/07357907.2012.756111     Document Type: Article

References (133)

1. Carlier MF, Didry D, Erk I, Lepault J, Van Troys ML, Vandekerckhove J, Perelroizen I, Yin H, Doi Y, Pantaloni D. Tβ4 is not a simple G-actin sequestering protein and interacts with Factin at high concentration. J Biol Chem 1996;271(16):9231- 9239.
2. Dedova IV, Nikolaeva OP, Safer D, De La Cruz EM, dos Remedios CG. Thymosin β4 induces a conformational change in actin monomers. Biophys J 2006;90(3):985-992.
3. Yarmola EG, Klimenko ES, Fujita G, Bubb MR. Thymosin β4: actin regulation and more. Ann NY Acad Sci 2007;1112:76-85.
4. Grant DS, Kinsella JL, Kibbey MC, LaFlamme S, Burbelo PD, Goldstein AL, Kleinman HK. Matrigel induces thymosin β4 gene in differentiating endothelial cells. J Cell Sci 1995;108(Pt 12):3685-3694. (Pubitemid 26003202)
5. Grant DS, Rose W, Yaen C, Goldstein A, Martinez J, Kleinman H.Thymosin β4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis 1999;3(2):125-135. (Pubitemid 129644639)
6. Malinda KM, Goldstein AL, Kleinman HK.Thymosin β4 stimulates directional migration of human umbilical vein endothelial cells. FASEB J 1997;11(6):474-481. (Pubitemid 27259989)
7. Kraehenbuehl TP, Ferreira LS, Zammaretti P,Hubbell JA, Langer R. Cell-responsive hydrogel for encapsulation of vascular cells. Biomaterials 2009;30(26):4318-4324.
8. Chiu LL, Radisic M. Controlled release of thymosin β4 using collagen-chitosan composite hydrogels promotes epicardial cell migration and angiogenesis. J Control Release 2011;155(3):376-385.
9. Oh IS, So SS, Jahng KY, KimHG.Hepatocyte growth factor upregulates thymosin β4 in human umbilical vein endothelial cells. Biochem Biophys Res Commun 2002;296(2):401-405.
10. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK. The actin binding site on thymosin β4 promotes angiogenesis. FASEB J 2003;17(14):2103-2105.
11. Cierniewski CS, Malinowski M, Bednarek R, Cierniewska- Cieslak A. Adhesive and proteolytic phenotype of migrating endothelial cells induced by thymosin β4. Ann NY Acad Sci 2007;1112:123-139. (Pubitemid 47598658)
12. Philp D, Scheremeta B, Sibliss K, Zhou M, Fine EL, Nguyen M, Wahl L, Hoffman MP, Kleinman HK. Thymosin β4 promotes matrix metalloproteinase expression during wound repair. J Cell Physiol 2006;208(1):195-200. (Pubitemid 43849005)
13. Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 2004;432(7016):466-472. (Pubitemid 39576522)
14. Fan Y, Gong Y, Ghosh PK, Graham LM, Fox PL. Spatial coordination of actin polymerization and ILK-Akt2 activity during endothelial cell migration. Dev Cell 2009;16(5):661- 674.
15. Freeman KW, Bowman BR, Zetter BR. Regenerative protein thymosin β4 is a novel regulator of purinergic signaling. FASEB J 2011;25(3):907-915.
16. Selmi A,MalinowskiM, BrutkowskiW, BednarekR, Cierniewski CS. Thymosin β4 promotes the migration of endothelial cells without intracellular Ca2+ elevation. Exp Cell Res 2012;318(14):1659-666.
17. Qiu FY, Song XX, Zheng H, Zhao YB, Fu GS. Thymosin β4 induces endothelial progenitor cell migration via PI3K/Akt/eNOS signal transduction pathway. J Cardiovasc Pharmacol 2009;53(3):209-214.
18. Kupatt C, Bock-Marquette I, Boekstegers P. Embryonic endothelial progenitor cell-mediated cardioprotection requires Thymosin β4. Trends Cardiovasc Med 2008;18(6):205-210.
19. Hinkel R, El-Aouni C, Olson T, Horstkotte J, Mayer S, Muller S, Willhauck M, Spitzweg C, Gildehaus FJ,MunzingW,Hannappel E, Bock-Marquette I, DiMaio JM, Hatzopoulos AK, Boekstegers P, Kupatt C.Thymosin β4 is an essential paracrine factor of embryonic endothelial progenitor cell-mediated cardioprotection. Circulation 2008;117(17):2232-2240.
20. Bock-Marquette I, Shrivastava S, Pipes GC,Thatcher JE, Blystone A, Shelton JM, Galindo CL, Melegh B, Srivastava D, Olson EN, DiMaio JM. Thymosin β4 mediated PKC activation is essential to initiate the embryonic coronary developmental program and epicardial progenitor cell activation in adult mice in vivo. J Mol Cell Cardiol 2009;46(5):728-738.
21. Lee SH, Son MJ, Oh SH, Rho SB, Park K, Kim YJ, Park MS, Lee JH. Thymosin β10 inhibits angiogenesis and tumor growth by interfering with Ras function. Cancer Res 2005;65(1):137- 148.
22. Mu H, Ohashi R, Yang H, Wang X, Li M, Lin P, Yao Q, Chen C. Thymosin β10 inhibits cell migration and capillary-like tube formation of human coronary artery endothelial cells. CellMotil Cytoskeleton 2006;63(4):222-230.
23. Zhang T, Li X, Yu W, Yan Z, Zou H, He X. Overexpression of thymosin β10 inhibits VEGF mRNA expression, autocrine VEGF protein production, and tube formation in hypoxiainduced monkey choroid-retinal endothelial cells. Ophthalmic Res 2009;41(1):36-43.
24. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu JD, Srivastava D. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 2012;485(7400):593-598.
25. Yesilay AB, Karakurt O, Akdemir R, Erden G, Kilic H, Acikel S, Karasu B, Sari M, Balci M, Aksoy M. Thymosin β4 levels after successful primary percutaneous coronary intervention for acute myocardial infarction. Turk Kardiyol Dern Ars 2011;39(8):654-660.
26. Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR. Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization. Nature 2007;445(7124):177-182. (Pubitemid 46095717)
27. Smart N, Risebro CA,Melville AA,Moses K, Schwartz RJ, Chien KR, Riley PR.Thymosin β4 is essential for coronary vessel development and promotes neovascularization via adult epicardium. Ann NY Acad Sci 2007;1112:171-188. (Pubitemid 47598641)
28. Banerjee I, Zhang J, Moore-Morris T, Lange S, Shen T, Dalton ND, Gu Y, Peterson KL, Evans SM, Chen J.Thymosin β4 is dispensable formurine cardiac development and function. Circ Res 2012;110(3):456-464.
29. Gajzer DC, Balbin J, Chaudhry HW. Thymosin β4 and cardiac Regeneration: Are we missing a beat? Stem Cell Rev 2012, doi: 10.1007/s12015-012-9378-3.
30. Smart N, Hill AA, Cross JC, Riley PR. A differential screen for putative targets of the bHLH transcription factor Hand1 in cardiac morphogenesis. Mech Dev 2002; 119(Suppl 1): S65-S71. (Pubitemid 39658687)
31. Smart N, Dube KN, Riley PR. Identification of Thymosin β4 as an effector of Hand1-mediated vascular development. Nat Commun 2010;1:46.
32. Shrivastava S, Srivastava D, Olson EN, DiMaio JM, Bock- Marquette I.Thymosin β4 and cardiac repair. Ann NY Acad Sci 2010;1194:87-96.
33. Roth LW, Bormann P,Wiederkehr C, Reinhard E. β-thymosin, a modulator of the actin cytoskeleton is increased in regenerating retinal ganglion cells. Eur J Neurosci 1999;11(10):3488-3498. (Pubitemid 29484246)
34. Roth LW, Bormann P, Bonnet A, Reinhard E. β-thymosin is required for axonal tract formation in developing zebrafish brain. Development 1999;126(7):1365-1374. (Pubitemid 29195226)
35. Xiong Y,Mahmood A,Meng Y, Zhang Y, Zhang ZG,MorrisDC, ChoppM. Treatment of traumatic brain injury with thymosin β4 in rats. J Neurosurg 2011;114(1):102-115.
36. Xiong Y, Zhang Y,Mahmood A,Meng Y, Zhang ZG,MorrisDC, Chopp M. Neuroprotective and neurorestorative effects of thymosin β4 treatment initiated 6 hours after traumatic brain injury in rats. J Neurosurg 2012;116(5):1081-1092.
37. Border BG, Lin SC, GriffinWS, Pardue S, Morrison-BogoradM. Alterations in actin-binding β-thymosin expression accompany neuronal differentiation and migration in rat cerebellum. J Neurochem 1993;61(6):2104-2114.
38. Choe J, Sun W, Yoon SY, Rhyu IJ, Kim EH, Kim H. Effect of thymosin β15 on the branching of developing neurons. Biochem Biophys Res Commun 2005;331(1):43-49. (Pubitemid 40545139)
39. Yang H, Cheng X, Yao Q, Li J, Ju G. The promotive effects of thymosin β4 on neuronal survival and neurite outgrowth by upregulating L1 expression. Neurochem Res 2008;33(11):2269-2280.
40. Mollinari C, Ricci-Vitiani L, Pieri M, Lucantoni C, Rinaldi AM, Racaniello M, De Maria R, Zona C, Pallini R, Merlo D, Garaci E. Downregulation of thymosin β4 in neural progenitor grafts promotes spinal cord regeneration. J Cell Sci 2009;122(Pt 22):4195-4207.
41. van Kesteren RE, Carter C, Dissel HM, van Minnen J, Gouwenberg Y, Syed NI, Spencer GE, Smit AB. Local synthesis of actinbinding protein β-thymosin regulates neurite outgrowth. J Neurosci 2006;26(1):152-157. (Pubitemid 43090916)
42. Golla R, Philp N, Safer D, Chintapalli J, Hoffman R, Collins L, Nachmias VT. Co-ordinate regulation of the cytoskeleton in 3T3 cells overexpressing thymosin-β4. Cell Motil Cytoskeleton 1997;38(2):187-200. (Pubitemid 27430424)
43. PhilpD,KleinmanHK. Animal studieswith thymosin β,amultifunctional tissue repair and regeneration peptide. Ann NY Acad Sci 2010;1194:81-86.
44. Li X, Zheng L, Peng F, Qi C, Zhang X, Zhou A, Liu Z, Wu S. Recombinant thymosin β4 can promote full-thickness cutaneous wound healing. Protein Expr Purif 2007;56(2):229-236. (Pubitemid 350011045)
45. Malinda KM, Sidhu GS, Mani H, Banaudha K, Maheshwari RK, Goldstein AL, Kleinman HK. Thymosin β4 accelerates wound healing. J Invest Dermatol 1999;113(3):364-368.
46. Goldstein AL, Hannappel E, Kleinman HK.Thymosin β4: actinsequestering proteinmoonlights to repair injured tissues. Trends Mol Med 2005;11(9):421-429. (Pubitemid 41254045)
47. Francis Godschalk M. Pressure ulcers: a role for thymosin β4. Ann NY Acad Sci 2007;1112:413-417.
48. Guarnera G, DE Rosa A, Camerini R.Thymosin β4 and venous ulcers: clinical remarks on a European prospective, randomized study on safety, tolerability, and enhancement on healing. Ann NY Acad Sci 2007;1112:407-412. (Pubitemid 47598644)
49. Treadwell T, Kleinman HK, Crockford D, HardyMA, Guarnera GT, Goldstein AL.The regenerative peptide thymosin β4 accelerates the rate of dermal healing inpreclinical animalmodels and in patients. Ann NY Acad Sci 2012;1270:37-44.
50. Philp D, Badamchian M, Scheremeta B, Nguyen M, Goldstein AL, Kleinman HK. Thymosin β4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound Repair Regen 2003;11(1):19-24. (Pubitemid 36268605)
51. Ehrlich HP, Hazard SW, 3rd. Thymosin β4 enhances repair by organizing connective tissue and preventing the appearance of myofibroblasts. Ann NY Acad Sci 2010;1194:118-124.
52. Huang CM, Wang CC, Barnes S, Elmets CA. In vivo detection of secreted proteins from wounded skin using capillary ultrafiltration probes and mass spectrometric proteomics. Proteomics 2006;6(21):5805-5814. (Pubitemid 44764017)
53. Philp D, Goldstein AL, Kleinman HK.Thymosin β4 promotes angiogenesis, wound healing, and hair follicle development. Mech Ageing Dev 2004;125(2):113-115. (Pubitemid 38177569)
54. Philp D, Nguyen M, Scheremeta B, St-Surin S, Villa AM, Orgel A, Kleinman HK, Elkin M. Thymosin β4 increases hair growth by activation of hair follicle stem cells. FASEB J 2004;18(2): 385-387.
55. Philp D, St-Surin S, ChaHJ, Moon HS, KleinmanHK, ElkinM. Thymosin β4 induces hair growth via stem cell migration and differentiation. Ann NY Acad Sci 2007;1112:95-103. (Pubitemid 47598650)
56. Sosne G, Chan CC, Thai K, Kennedy M, Szliter EA, Hazlett LD, Kleinman HK. Thymosin β4 promotes corneal wound healing and modulates inflammatory mediators in vivo. Exp Eye Res 2001;72(5):605-608. (Pubitemid 32977230)
57. Sosne G, Szliter EA, Barrett R, Kernacki KA, Kleinman H, Hazlett LD.Thymosin β4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res 2002;74(2):293-299. (Pubitemid 34948404)
58. SosneG, Siddiqi A,Kurpakus-Wheater M.Thymosin-β4 inhibits corneal epithelial cell apoptosis after ethanol exposure in vitro. Invest Ophthalmol Vis Sci 2004;45(4):1095-1100. (Pubitemid 38869013)
59. Sosne G, Qiu P, Kurpakus-Wheater M. Thymosin β4 and the eye: I can see clearly now the pain is gone. Ann NY Acad Sci 2007;1112:114-122. (Pubitemid 47598645)
60. Sosne G, Qiu P, Kurpakus-Wheater M. Thymosin β4: A novel corneal wound healing and anti-inflammatory agent. Clin Ophthalmol 2007;1(3):201-207.
61. Sosne G, Qiu P, Kurpakus-Wheater M, Matthew H. Thymosin β4 and corneal wound healing: visions of the future. Ann NY Acad Sci 2010;1194:190-198.
62. Dunn SP, Heidemann DG, Chow CY, Crockford D, Turjman N, Angel J, Allan CB, Sosne G. Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin β4. Ann NY Acad Sci 2010;1194:199-206.
63. Sosne G, Hafeez S, Greenberry AL, 2nd, Kurpakus-Wheater M. Thymosin β4 promotes human conjunctival epithelial cell migration. Curr Eye Res 2002;24(4):268-273. (Pubitemid 35155742)
64. Sosne G, Xu L, Prach L, Mrock LK, Kleinman HK, Letterio JJ, Hazlett LD, Kurpakus-Wheater M. Thymosin β4 stimulates laminin-5 production independent of TGF-b. Exp Cell Res 2004;293(1):175-183. (Pubitemid 38064424)
65. QiuP, Kurpakus-WheaterM, SosneG.Matrixmetalloproteinase activity is necessary for thymosin β4 promotion of epithelial cell migration. J Cell Physiol 2007;212(1):165-173. (Pubitemid 46867598)
66. Roy P, Rajfur Z, Jones D,Marriott G, Loew L, Jacobson K. Local photorelease of caged thymosin β4 in locomoting keratocytes causes cell turning. J Cell Biol 2001;153(5):1035-1048.
67. Wang WS, Chen PM, Hsiao HL, Ju SY, Su Y. Overexpression of the thymosin β4 gene is associated with malignant progression of SW480 colon cancer cells. Oncogene 2003;22(21): 3297-3306. (Pubitemid 36712942)
68. Wang WS, Chen PM, Hsiao HL, Wang HS, Liang WY, Su Y. Overexpression of the thymosin β4 gene is associated with increased invasion of SW480 colon carcinoma cells and the distant metastasis of human colorectal carcinoma. Oncogene 2004;23(39):6666-6671. (Pubitemid 39265530)
69. Jain AK, Moore SM, Yamaguchi K, Eling TE, Baek SJ. Selective nonsteroidal anti-inflammatory drugs induce thymosin β4 and alter actin cytoskeletal organization in human colorectal cancer cells. J Pharmacol ExpTher 2004;311(3):885-891. (Pubitemid 39612692)
70. Huang HC, Hu CH, Tang MC, Wang WS, Chen PM, Su Y. Thymosin β4 triggers an epithelial-mesenchymal transition incolorectal carcinoma by upregulating integrin-linked kinase. Oncogene 2007;26(19):2781-290.
71. Tang MC, Chan LC, Yeh YC, Chen CY, Chou TY,WangWS, Su Y.Thymosin β4 induces colon cancer cell migration and clinical metastasis via enhancing ILK/IQGAP1/Rac1 signal transduction pathway. Cancer Lett 2011;308(2):162-171.
72. Ricci-Vitiani L, Mollinari C, di Martino S, Biffoni M, Pilozzi E, Pagliuca A, de StefanoMC, Circo R,Merlo D,DeMaria R,Garaci E.Thymosin β4 targeting impairs tumorigenic activity of colon cancer stem cells. FASEB J 2010;24(11):4291-4301.
73. Hsiao HL, Wang WS, Chen PM, Su Y. Overexpression of thymosin β4 renders SW480 colon carcinoma cellsmore resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively. Carcinogenesis 2006;27(5):936-944.
74. Nemolato S, Restivo A, Cabras T, Coni P, Zorcolo L, Orru G, Fanari M, Cau F, Gerosa C, Fanni D, Messana I, Castagnola M, Casula G, Faa G. Thymosin β4 in colorectal cancer is localized predominantly at the invasion front in tumor cells undergoing epithelial mesenchymal transition. Cancer Biol Ther 2012;13(4):191-197.
75. Cierniewski CS, Papiewska-Pajak I, Malinowski M, Sacewicz- Hofman I, Wiktorska M, Kryczka J, Wysocki T, Niewiarowska J, Bednarek R. Thymosin β4 regulates migration of colon cancer cells by a pathway involving interaction with Ku80. Ann NY Acad Sci 2010;1194:60-71.
76. Ryu YK, Lee YS, Lee GH, Song KS, Kim YS, Moon EY. Regulation of glycogen synthase kinase-3 by thymosin β4 is associated with gastric cancer cell migration. Int J Cancer 2012;131(9):2067-2077.
77. Nummela P, Yin M, Kielosto M, Leaner V, Birrer MJ, Holtta E. Thymosin β4 is a determinant of the transformed phenotype and invasiveness of S-adenosylmethionine decarboxylasetransfected fibroblasts. Cancer Res 2006;66(2):701-712. (Pubitemid 43165932)
78. Cha HJ, Jeong MJ, Kleinman HK. Role of thymosin β4 in tumor metastasis and angiogenesis. J Natl Cancer Inst 2003;95(22):1674-1680. (Pubitemid 37509076)
79. Jo JO, Kim SR, Bae MK, Kang YJ, Ock MS, Kleinman HK, Cha HJ. Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1alpha-dependent manner. Biochim Biophys Acta 2010;1803(11):1244-1251.
80. Hardesty WM, Kelley MC, Mi D, Low RL, Caprioli RM. Protein signatures for survival and recurrence in metastatic melanoma. J Proteomics 2011;74(7):1002-1014.
81. Oh JM, Moon EY. Actin-sequestering protein, thymosin β4, induces paclitaxel resistance through ROS/HIF-1alpha stabilization in HeLa human cervical tumor cells. Life Sci 2010;87(9-10):286-293.
82. Moon EY, Im YS, Ryu YK, Kang JH. Actin-sequestering protein, thymosin β4, is a novel hypoxia responsive regulator. Clin Exp Metast 2010;27(8):601-609.
83. Ryu YK, Im YS, Moon EY. Cooperation of actin-sequestering protein, thymosin β4 and hypoxia inducible factor-1α in tumor cell migration. Oncol Rep 2010;24(5):1389-1394.
84. Kim A, Son M, Kim KI, Yang Y, Song EY, Lee HG, Lim JS. Elevation of intracellular cyclic AMP inhibits NF-κB-mediated thymosin β4 expression in melanoma cells. Exp Cell Res 2009;315(19):3325-3335.
85. Chiappetta G, Pentimalli F, Monaco M, Fedele M, Pasquinelli R, Pierantoni GM, Ribecco MT, Santelli G, Califano D, Pezzullo L, Fusco A. Thymosin β10 gene expression as a possible tool in diagnosis of thyroid neoplasias. Oncol Rep 2004;12(2): 239-243.
86. Feher LZ, Pocsay G, Krenacs L, Zvara A, Bagdi E, Pocsay R, Lukacs G, Gyory F, Gazdag A, Tarko E, Puskas LG. Amplification of thymosin β10 and AKAP13 genes in metastatic and aggressive papillary thyroid carcinomas. Pathol Oncol Res 2012;18(2):449-458.
87. Conlon JM, Grimelius L, Wallin G, Thim L. Isolation and structural characterization of thymosin-β4 from a human medullary thyroid carcinoma. J Endocrinol 1988;118(1):155- 159.
88. Liu JM, Kusinski M, Ilic V, Bignon J, Hajem N, Komorowski J, Kuzdak K, StepienH,Wdzieczak-Bakala J.Overexpression of the angiogenic tetrapeptide AcSDKP in human malignant tumors. Anticancer Res 2008;28(5A):2813-2817.
89. Califano D, Monaco C, Santelli G, Giuliano A, Veronese ML, Berlingieri MT, de Franciscis V, Berger N, Trapasso F, Santoro M, Viglietto G, Fusco A. Thymosin β10 gene overexpression correlated with the highly malignant neoplastic phenotype of transformed thyroid cells in vivo and in vitro. Cancer Res 1998;58(4):823-828. (Pubitemid 28099498)
90. Takano T, Hasegawa Y, Miyauchi A, Matsuzuka F, Yoshida H, Kuma K, Amino N. Quantitative analysis of thymosin β10 messenger RNA in thyroid carcinomas. Jpn J Clin Oncol 2002;32(7):229-232. (Pubitemid 43102804)
91. Santelli G, Bartoli PC, Giuliano A, Porcellini A,Mineo A, Barone MV, Busiello I, Trapasso F, Califano D, Fusco A. Thymosin β10 protein synthesis suppression reduces the growth of human thyroid carcinoma cells in semisolid medium. Thyroid 2002;12(9):765-772.
92. McDoniels-Silvers AL, Nimri CF, Stoner GD, Lubet RA, You M. Differential gene expression in human lung adenocarcinomas and squamous cell carcinomas. Clin Cancer Res 2002;8(4):1127-1138. (Pubitemid 35177366)
93. Gu Y, Wang C, Wang Y, Qiu X, Wang E. Expression of thymosin β10 and its role innon-small cell lung cancer.HumPathol 2009;40(1):117-124.
94. Lee SM, Na YK, Hong HS, Jang EJ, Yoon GS, Park JY, Kim DS. Hypomethylation of the thymosin β10 gene is not associated with its overexpression in non-small cell lung cancer. Mol Cells 2011;32(4):343-348.
95. Bao L, Loda M, Zetter BR. Thymosin β15 expression in tumor cell lines with varying metastatic potential. Clin ExpMetast 1998;16(3):227-233. (Pubitemid 28201990)
96. GuYM, Li SY,QiuXS,WangEH. Elevated thymosinβ15 expression is associated with progression and metastasis of non-small cell lung cancer. APMIS 2008; 116(6):484-490.
97. Verghese-Nikolakaki S, Apostolikas N, Livaniou E, Ithakissios DS, Evangelatos GP. Preliminary findings on the expression of thymosin β10 in human breast cancer. Br J Cancer 1996;74(9):1441-1444. (Pubitemid 26370737)
98. Liu CR, Ma CS, Ning JY, You JF, Liao SL, Zheng J. Differential thymosin β10 expression levels and actin filament organization in tumor cell lines with different metastatic potential. Chin Med J 2004;117(2):213-218. (Pubitemid 38351446)
99. Maelan AE, Rasmussen TK, Larsson LI. Localization of thymosin β10 in breast cancer cells: relationship to actin cytoskeletal remodeling and cell motility. Histochem Cell Biol 2007;127(1):109-113. (Pubitemid 46011325)
100. Larsson LI,Holck S.Occurrence of thymosin β4 inhumanbreast cancer cells and in other cell types of the tumor microenvironment. Hum Pathol 2007;38(1):114-119.
101. Gold JS, Bao L, Ghoussoub RA, Zetter BR, Rimm DL. Localization and quantitation of expression of the cell motilityrelated protein thymosin β15 in human breast tissue.Mod Pathol 1997;10(11):1106-1112.
102. Lee SH, Zhang W, Choi JJ, Cho YS, Oh SH, Kim JW, Hu L, Xu J, Liu J, Lee JH. Overexpression of the thymosin β10 gene in human ovarian cancer cells disrupts F-actin stress fiber and leads to apoptosis. Oncogene 2001;20(46):6700-6706. (Pubitemid 33020598)
103. Yamamoto T, Gotoh M, Kitajima M, Hirohashi S. Thymosin β4 expression is correlated with metastatic capacity of colorectal carcinomas. Biochem Biophys Res Commun 1993;193(2):706-710. (Pubitemid 23214285)
104. Kim NS, Kang YJ, Jo JO, Kim HY, Oh YR, Kim YO, Jung MH, Ock MS, Cha HJ. Elevated expression of thymosin β4, vascularendothelial growth factor (VEGF), and hypoxia inducible factor (HIF)-1alpha in early-stage cervical cancers. Pathol Oncol Res 2011;17(3):493-502.
105. Moon HS, Even-Ram S, Kleinman HK, Cha HJ. Zyxin is upregulated in the nucleus by thymosin β4 in SiHa cells. Exp Cell Res 2006;312(17):3425-3431. (Pubitemid 44380242)
106. Oh SY, Song JH, Gil JE, Kim JH, Yeom YI, Moon EY. ERK activation by thymosin-β4 (TB4) overexpression induces paclitaxelresistance. Exp Cell Res 2006;312(9):1651-1657.
107. Oh JM, Ryoo IJ, Yang Y, Kim HS, Yang KH,Moon EY. Hypoxiainducible transcription factor (HIF)-1 alpha stabilization by actin-sequestering protein, thymosin β4 (Tβ4) in Hela cervical tumor cells. Cancer Lett 2008;264(1):29-35.
108. Huang L, Zheng M, ZhouQM, Zhang MY, JiaWH, Yun JP,Wang HY. Identification of a gene-expression signature for predicting lymph node metastasis in patients with early stage cervical carcinoma. Cancer 2011;117(15):3363-3373.
109. Dhaese S, Jonckheere V, Goethals M,Waltregny D, Vandekerckhove J, Ampe C, Van Troys M. Functional and profiling studies prove that prostate cancer upregulated neuroblastoma thymosin β is the true human homologue of rat thymosin β15. FEBS Lett 2007;581(25):4809-4815. (Pubitemid 47531747)
110. Banyard J, Barrows C, Zetter BR. Differential regulation of human thymosin β15 isoforms by transforming growth factor β1. Genes Chromosomes Canc 2009;48(6):502-509.
111. Bao L, Loda M, Janmey PA, Stewart R, Anand-Apte B, Zetter BR. Thymosin β15: a novel regulator of tumor cell motility upregulated in metastatic prostate cancer. Nat Med 1996;2(12):1322-1328. (Pubitemid 26401734)
112. Banyard J, Hutchinson LM, Zetter BR. Thymosin β-NB is the human isoform of rat thymosin β15. Ann NY Acad Sci 2007;1112:286-296.
113. Chakravatri A, Zehr EM, Zietman AL, Shipley WU, Goggins WB, Finkelstein DM, Young RH, Chang EL, Wu CL. Thymosin β15 predicts for distant failure in patients with clinically localized prostate cancer-results froma pilot study.Urology 2000;55(5):635-638.
114. Iguchi K, Ito M, Usui S, Mizokami A, Namiki M, Hirano K. Downregulation of thymosin β4 expression by androgen in prostate cancer LNCaP cells. J Androl 2008;29(2):207-212. (Pubitemid 351345718)
115. Kobayashi T, Okada F, Fujii N, Tomita N, Ito S, Tazawa H, Aoyama T, Choi SK, Shibata T, Fujita H, Hosokawa M. Thymosin-β4 regulates motility and metastasis of malignant mouse fibrosarcoma cells. Am J Pathol 2002;160(3):869-882. (Pubitemid 34224577)
116. Santelli G, Califano D, Chiappetta G, Vento MT, Bartoli PC, Zullo F, Trapasso F, Viglietto G, Fusco A. Thymosin β10 gene overexpression is a general event in human carcinogenesis. Am J Pathol 1999;155(3):799-804. (Pubitemid 29426825)
117. Zhang Y, Feurino LW, Zhai Q, Wang H, Fisher WE, Chen C, Yao Q, Li M.Thymosin β4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation. Cancer BiolTher 2008;7(3): 419-423. (Pubitemid 351847060)
118. Alldinger I, Dittert D, Peiper M, Fusco A, Chiappetta G, Staub E, Lohr M, Jesnowski R, Baretton G, Ockert D, Saeger HD, Grutzmann R, Pilarsky C. Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer. Pancreatology 2005;5(4-5):370-379. (Pubitemid 41160274)
119. Li M, Zhang Y, Zhai Q, Feurino LW, FisherWE, Chen C, Yao Q. Thymosin β10 is aberrantly expressed in pancreatic cancer and induces JNK activation. Cancer Invest 2009;27(3):251-256.
120. Hall AK. Differential expression of thymosin genes in human tumors and in the developing human kidney. Int J Cancer 1991;48(5):672-677.
121. Hall AK. Amplification-independent overexpression of thymosin β10 mRNA in human renal cell carcinoma. Ren Fail 1994;16(2):243-254. (Pubitemid 24347260)
122. Wang AG, Yoon SY, Oh JH, Jeon YJ, Kim M, Kim JM, Byun SS, Yang JO, Kim JH, Kim DG, Yeom YI, Yoo HS, Kim YS, Kim NS. Identification of intrahepatic cholangiocarcinoma related genes by comparison with normal liver tissues using expressed sequence tags. Biochem Biophys Res Commun 2006;345(3):1022-1032. (Pubitemid 43776521)
123. Sardi I, Tintori V, Marchi C, Veltroni M, Lippi A, Tucci F, Tamburini A, Bernini G, Faulkner L. Molecular profiling of high-risk neuroblastoma by cDNA array. Int J Mol Med 2002;9(5):541-545.
124. Wang ZY, Zeng FQ, Zhu ZH, Jiang GS, Lv L, Wan F, Dong R, Xiao XY, Xing SA. Evaluation of thymosin β4 in the regulation of epithelial-mesenchymal transformation in urothelial carcinoma. Urol Oncol 2012;30(2):167-176.
125. Akhter M, Kobayashi I, Kiyoshima T, Matsuo K, Yamaza H, Wada H, Honda JY, Ming X, Sakai H. Possible functional involvement of thymosin β4 in developing tooth germ of mouse lower first molar. Histochem Cell Biol 2005;124(3-4):207-213. (Pubitemid 41624205)
126. Cha HJ, Philp D, Lee SH, Moon HS, Kleinman HK, Nakamura T. Over-expression of thymosin β4 promotes abnormal tooth development and stimulation of hair growth. Int J Dev Biol 2010;54(1):135-140.
127. Barnaeva E, Nadezhda A, Hannappel E, Sjogren MH, Rojkind M. Thymosin β4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF- β receptor in human hepatic stellate cells. Ann NY Acad Sci 2007;1112:154-160. (Pubitemid 47598673)
128. Reyes-Gordillo K, Shah R, Popratiloff A, Fu S,Hindle A, Brody F, Rojkind M.Thymosin β4 (Tβ4) blunts PDGF-dependent phosphorylation and binding of AKT to actin in hepatic stellate cells. Am J Pathol 2011;178(5):2100-2108.
129. Leeanansaksiri W, DeSimone SK, Huff T, Hannappel E, Huff TF. Thymosin β4 and its N-terminal tetrapeptide, AcSDKP, inhibit proliferation, and induce dysplastic, non-apoptotic nuclei and degranulation of mast cells. Chem Biodivers 2004;1(7):1091-1100.
130. Leslie M. Mast cells show their might. Science 2007;317(5838):614-616.
131. Wyczolkowska J,Walczak-Drzewiecka A,Wagner W, Dastych J. Thymosin β4 andthymosinβ4-derived peptides inducemast cell exocytosis. Peptides 2007;28(4):752-759. (Pubitemid 46349334)
132. Tokura Y, Nakayama Y, Fukada S, Nara N, Yamamoto H, Matsuda R, Hara T. Muscle injury-induced thymosin β4 acts as a chemoattractant for myoblasts. J Biochem 2011;149(1):43-48.
133. Silva WA, Jr, Covas DT, Panepucci RA, Proto-Siqueira R, Siufi JL, Zanette DL, Santos AR, Zago MA. The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells 2003;21(6):661-669. (Pubitemid 37329159)