Targeting protein tyrosine phosphatases for anticancer drug discovery

Current Pharmaceutical Design

Volumn 16, Issue 16, 2010, Pages 1843-1862

  Scott, Latanya M ^a,b   Lawrence, Harshani R ^a,b   Sebti, Saïd M ^a,b   Lawrence, Nicholas J ^a,b   Wu, Jie ^a,b  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

Author keywords

Cdc14; Cdc25; Eya; LMW PTP; PRL 3; Protein tyrosine phosphatase inhibitor; PTP1B; Shp2

Indexed keywords

4 THIAZOLIDINONE DERIVATIVE; ANTINEOPLASTIC AGENT; BN 82002; BN 82685; DEBIO 0931; ERTIPROTAFIB; FERRUGINOL; FLAVONOID; FURANODICTINE; GINKGETIN; IRC 083864; LOW MOLECULAR WEIGHT HEPARIN; MORIN; MSI 1436; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 3; NSC 117199; NSC 663284; NSC 87877; PHOSPHOPROTEIN PHOSPHATASE CDC14; PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE 1B; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; PROTEIN TYROSINE PHOSPHATASE SHP 2; SCIADOPTYSIN; TRODUSQUEMINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GROWTH; CLINICAL TRIAL; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG INHIBITION; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; DRUG WITHDRAWAL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; UNSPECIFIED SIDE EFFECT;

ANIMALS; ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; ISOENZYMES; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 11; PROTEIN TYROSINE PHOSPHATASES;

EID: 77953510496     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161210791209027     Document Type: Article

References (163)

1. Hunter T. Tyrosine phosphorylation: thirty years and counting. Curr Opin Cell Biol 2009; 21: 140-6.
2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100: 57-70.
3. Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy:oncogene and non-oncogene addiction. Cell 2009; 136: 823-37.
4. Ostman A, Hellberg C, Bohmer FD. Protein-tyrosine phosphatasesand cancer. Nat Rev Cancer 2006; 6: 307-20.
5. Tonks NK. Protein tyrosine phosphatases: from genes, to function,to disease. Nat Rev Mol Cell Biol 2006; 7: 833-46.
6. Bialy L, Waldmann H. Inhibitors of protein tyrosine phos-phatases:next-generation drugs? Angew Chem Int Ed Engl 2005; 44: 3814-39.
7. Jiang ZX, Zhang ZY. Targeting PTPs with small molecule inhi-bitors in cancer treatment. Cancer Metastasis Rev 2008; 27: 263-72.
8. Tautz L, Pellecchia M, Mustelin T. Targeting the PTPome inhuman disease. Expert Opin Ther Targets 2006; 10: 157-77.
9. Vintonyak VV, Antonchick AP, Rauh D, Waldmann H. Thetherapeutic potential of phosphatase inhibitors. Curr Opin ChemBiol 2009; 13: 272-83.
10. Alonso A, Sasin J, Bottini N, Friedberg I, Friedberg I, Osterman A, et al. Protein tyrosine phosphatases in the human genome. Cell 2004; 117: 699-711.
11. Andersen JN, Mortensen OH, Peters GH, Drake PG, Iversen LF, Olsen OH, et al. Structural and evolutionary relationships amongprotein tyrosine phosphatase domains. Mol Cell Biol 2001; 21:7117-36.
12. Lazo JS, Wipf P. Is Cdc25 a druggable target? Anticancer AgentsMed Chem 2008; 8: 837-42.
13. Andersen JN, Jansen PG, Echwald SM, Mortensen OH, Fukada T, Del Vecchio R, et al. A genomic perspective on protein tyrosinephosphatases: gene structure, pseudogenes, and genetic diseaselinkage. FASEB J 2004; 18: 8-30.
14. Tautz L, Mustelin T. Strategies for developing protein tyrosinephosphatase inhibitors. Methods 2007; 42: 250-60.
15. Poon RY, Hunter T. Dephosphorylation of Cdk2 Thr160 by thecyclin-dependent kinase-interacting phosphatase KAP in theabsence of cyclin. Science 1995; 270: 90-3.
16. Lee SW, Reimer CL, Fang L, Iruela-Arispe ML, Aaronson SA. Overexpression of kinase-associated phosphatase (KAP) in breastand prostate cancer and inhibition of the transformed phenotype byantisense KAP expression. Mol Cell Biol 2000; 20: 1723-32.
17. Yu Y, Jiang X, Schoch BS, Carroll RS, Black PM, Johnson MD. Aberrant splicing of cyclin-dependent kinase-associated proteinphosphatase KAP increases proliferation and migration inglioblastoma. Cancer Res 2007; 67: 130-8.
18. D'Angiolella V, Costanzo V, Gottesman ME, Avvedimento EV, Gautier J, Grieco D. Role for cyclin-dependent kinase 2 in mitosisexit. Curr Biol 2001; 11: 1221-6.
19. Bessette DC, Qiu D, Pallen CJ. PRL PTPs: mediators and markersof cancer progression. Cancer Metastasis Rev 2008; 27: 231-52.
20. Kikawa KD, Vidale DR, Van Etten RL, Kinch MS. Regulation ofthe EphA2 kinase by the low molecular weight tyrosine phos-phatase induces transformation. J Biol Chem 2002; 277: 39274-9.
21. Chiarugi P, Taddei ML, Schiavone N, Papucci L, Giannoni E, Fiaschi T, et al. LMW-PTP is a positive regulator of tumor onsetand growth. Oncogene 2004; 23: 3905-14.
22. Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, et al. WSTF regulates the H2A.X DNA damageresponse via a novel tyrosine kinase activity. Nature 2009; 457: 57-62.
23. Cook PJ, Ju BG, Telese F, Wang X, Glass CK, Rosenfeld MG. Tyrosine dephosphorylation of H2AX modulates apoptosis andsurvival decisions. Nature 2009; 458: 591-6.
24. Krishnan N, Jeong DG, Jung SK, Ryu SE, Xiao A, Allis CD, et al. Dephosphorylation of the C-terminal tyrosyl residue of the DNAdamage-related histone H2A.X is mediated by the proteinphosphatase eyes absent. J Biol Chem 2009; 284: 16066-70.
25. MacKeigan JP, Murphy LO, Blenis J. Sensitized RNAi screen ofhuman kinases and phosphatases identifies new regulators ofapoptosis and chemoresistance. Nat Cell Biol 2005; 7: 591-600.
26. Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, et al. Large-scale structural analysis of the classicalhuman protein tyrosine phosphatome. Cell 2009; 136: 352-63.
27. Yang J, Liang X, Niu T, Meng W, Zhao Z, Zhou GW. Crystalstructure of the catalytic domain of protein-tyrosine phosphataseSHP-1. J Biol Chem 1998; 273: 28199-207.
28. Hellmuth K, Grosskopf S, Lum CT, Wurtele M, Roder N, vonKries JP, et al. Specific inhibitors of the protein tyrosinephosphatase Shp2 identified by high-throughput docking. Proc NatlAcad Sci USA 2008; 105: 7275-80.
29. Lawrence HR, Pireddu R, Chen L, Luo Y, Sung SS, Szymanski AM, et al. Inhibitors of Src homology-2 domain containing proteintyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J MedChem 2008; 51: 4948-56.
30. Salmeen A, Andersen JN, Myers MP, Tonks NK, Barford D. Molecular basis for the dephosphorylation of the activationsegment of the insulin receptor by protein tyrosine phosphatase 1B. Mol Cell 2000; 6: 1401-12.
31. Puius YA, Zhao Y, Sullivan M, Lawrence DS, Almo SC, Zhang ZY. Identification of a second aryl phosphate-binding site inprotein-tyrosine phosphatase 1B: a paradigm for inhibitor design. Proc Natl Acad Sci USA 1997; 94: 13420-5.
32. Sun JP, Fedorov AA, Lee SY, Guo XL, Shen K, Lawrence DS, et al. Crystal structure of PTP1B complexed with a potent andselective bidentate inhibitor. J Biol Chem 2003; 278: 12406-14.
33. Trapasso F, Drusco A, Costinean S, Alder H, Aqeilan RI, Iuliano R, et al. Genetic ablation of Ptprj, a mouse cancer susceptibilitygene, results in normal growth and development and does notpredispose to spontaneous tumorigenesis. DNA Cell Biol 2006; 25:376-82.
34. Scherr M, Chaturvedi A, Battmer K, Dallmann I, Schultheis B, Ganser A, et al. Enhanced sensitivity to inhibition of SHP2,STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood 2006; 107: 3279-87.
35. Neel BG, Gu H, Pao L. The 'Shp'ing news: SH2 domain-containingtyrosine phosphatases in cell signaling. Trends Biochem Sci 2003;28: 284-93.
36. Milarski KL, Saltiel AR. Expression of catalytically inactive Sypphosphatase in 3T3 cells blocks stimulation of mitogen-activatedprotein kinase by insulin. J Biol Chem 1994; 269: 21239-43.
37. Bennett AM, Hausdorff SF, O'Reilly AM, Freeman RM, Neel BG. Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression. Mol Cell Biol 1996; 16: 1189-202.
38. Imhof D, Wavreille AS, May A, Zacharias M, Tridandapani S, Pei D. Sequence specificity of SHP-1 and SHP-2 Src homology 2domains. Critical roles of residues beyond the pY+3 position. J Biol Chem 2006; 281: 20271-82.
39. Sweeney MC, Wavreille AS, Park J, Butchar JP, Tridandapani S, Pei D. Decoding protein-protein interactions through combinatorialchemistry: sequence specificity of SHP-1, SHP-2, and SHIP SH2domains. Biochemistry 2005; 44: 14932-47.
40. Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE. Crystalstructure of the tyrosine phosphatase SHP-2. Cell 1998; 92: 441-50.
41. Eck MJ, Pluskey S, Trub T, Harrison SC, Shoelson SE. Spatialconstraints on the recognition of phosphoproteins by the tandemSH2 domains of the phosphatase SH-PTP2. Nature 1996; 379: 277-80.
42. Cunnick JM, Mei L, Doupnik CA, Wu J. Phosphotyrosines 627 and659 of Gab1 constitute a bisphosphoryl tyrosine-based activationmotif (BTAM) conferring binding and activation of SHP2. J Biol Chem 2001; 276: 24380-7.
43. Ottinger EA, Botfield MC, Shoelson SE. Tandem SH2 domainsconfer high specificity in tyrosine kinase signaling. J Biol Chem 1998; 273: 729-35.
44. Pluskey S, Wandless TJ, Walsh CT, Shoelson SE. Potent stimu-lation of SH-PTP2 phosphatase activity by simultaneous occupancyof both SH2 domains. J Biol Chem 1995; 270: 2897-900.
45. Niu T, Liang X, Yang J, Zhao Z, Zhou GW. Kinetic comparison ofthe catalytic domains of SHP-1 and SHP-2. J Cell Biochem 1999;72: 145-50.
46. Mishra AK, Zhang A, Niu T, Yang J, Liang X, Zhao ZJ, et al. Substrate specificity of protein tyrosine phosphatase: differentialbehavior of SHP-1 and SHP-2 towards signal regulation proteinSIRP alpha1. J Cell Biochem 2002; 84: 840-6.
47. Shen K, Keng YF, Wu L, Guo XL, Lawrence DS, Zhang ZY. Acquisition of a specific and potent PTP1B inhibitor from a novelcombinatorial library and screening procedure. J Biol Chem 2001;276: 47311-9.
48. Cunnick JM, Meng S, Ren Y, Desponts C, Wang HG, Djeu JY, et al. Regulation of the mitogen-activated protein kinase signalingpathway by SHP2. J Biol Chem 2002; 277: 9498-504.
49. Hadari YR, Kouhara H, Lax I, Schlessinger J. Binding of Shp2tyrosine phosphatase to FRS2 is essential for fibroblast growthfactor-induced PC12 cell differentiation. Mol Cell Biol 1998; 18:3966-73.
50. Kuhne MR, Pawson T, Lienhard GE, Feng GS. The insulinreceptor substrate 1 associates with the SH2-containing phospho-tyrosine phosphatase Syp. J Biol Chem 1993; 268: 11479-81.
51. Myers MG Jr, Mendez R, Shi P, Pierce JH, Rhoads R, White MF. The COOH-terminal tyrosine phosphorylation sites on IRS-1 bindSHP-2 and negatively regulate insulin signaling. J Biol Chem 1998;273: 26908-14.
52. Ren Y, Meng S, Mei L, Zhao ZJ, Jove R, Wu J. Roles of Gab1 andSHP2 in paxillin tyrosine dephosphorylation and Src activation inresponse to epidermal growth factor. J Biol Chem 2004; 279: 8497-505.
53. Zhang SQ, Yang W, Kontaridis MI, Bivona TG, Wen G, Araki T, et al. Shp2 regulates SRC family kinase activity and Ras/Erkactivation by controlling Csk recruitment. Mol Cell 2004; 13: 341-55.
54. Agazie YM, Hayman MJ. Molecular mechanism for a role of SHP2in epidermal growth factor receptor signaling. Mol Cell Biol 2003;23: 7875-86.
55. Zhou X, Agazie YM. Molecular mechanism for SHP2 in promotingHER2-induced signaling and transformation. J Biol Chem 2009;284: 12226-34.
56. Cleghon V, Feldmann P, Ghiglione C, Copeland TD, Perrimon N, Hughes DA, et al. Opposing actions of CSW and RasGAPmodulate the strength of Torso RTK signaling in the Drosophilaterminal pathway. Mol Cell 1998; 2: 719-27.
57. Montagner A, Yart A, Dance M, Perret B, Salles JP, Raynal P. Anovel role for Gab1 and SHP2 in epidermal growth factor-inducedRas activation. J Biol Chem 2005; 280: 5350-60.
58. Hanafusa H, Torii S, Yasunaga T, Matsumoto K, Nishida E. Shp2,an SH2-containing protein-tyrosine phosphatase, positivelyregulates receptor tyrosine kinase signaling by dephosphorylatingand inactivating the inhibitor Sprouty. J Biol Chem 2004; 279:22992-5.
59. Fujioka Y, Matozaki T, Noguchi T, Iwamatsu A, Yamao T, Takahashi N, et al. A novel membrane glycoprotein, SHPS-1, thatbinds the SH2-domain-containing protein tyrosine phosphataseSHP-2 in response to mitogens and cell adhesion. Mol Cell Biol 1996; 16: 6887-99.
60. Jackson DE, Ward CM, Wang R, Newman PJ. The protein-tyrosinephosphatase SHP-2 binds platelet/endothelial cell adhesionmolecule-1 (PECAM-1) and forms a distinct signaling complexduring platelet aggregation. Evidence for a mechanistic linkbetween PECAM-1- and integrin-mediated cellular signaling. JBiol Chem 1997; 272: 6986-93.
61. Zhao R, Zhao ZJ. Dissecting the interaction of SHP-2 with PZR, animmunoglobulin family protein containing immunoreceptortyrosine-based inhibitory motifs. J Biol Chem 2000; 275: 5453-9.
62. Famiglietti SJ, Nakamura K, Cambier JC. Unique features of SHIP,SHP-1 and SHP-2 binding to FcgammaRIIb revealed by surfaceplasmon resonance analysis. Immunol Lett 1999; 68: 35-40.
63. Bertotti A, Comoglio PM, Trusolino L. Beta4 integrin activates aShp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth. J Cell Biol 2006; 175: 993-1003.
64. Wu TR, Hong YK, Wang XD, Ling MY, Dragoi AM, Chung AS, et al. SHP-2 is a dual-specificity phosphatase involved in Stat1dephosphorylation at both tyrosine and serine residues in nuclei. JBiol Chem 2002; 277: 47572-80.
65. You M, Yu DH, Feng GS. Shp-2 tyrosine phosphatase functions asa negative regulator of the interferon-stimulated Jak/STATpathway. Mol Cell Biol 1999; 19: 2416-24.
66. Zhou X, Coad J, Ducatman B, Agazie YM. SHP2 is up-regulated inbreast cancer cells and in infiltrating ductal carcinoma of the breast,implying its involvement in breast oncogenesis. Histopathology 2008; 53: 389-402.
67. Xu R, Yu Y, Zheng S, Zhao X, Dong Q, He Z, et al. Over-expression of Shp2 tyrosine phosphatase is implicated in leukemo-genesis in adult human leukemia. Blood 2005; 106: 3142-9.
68. Zhou XD, Agazie YM. Inhibition of SHP2 leads to mesenchymalto epithelial transition in breast cancer cells. Cell Death Differ 2008; 15: 988-96.
69. Agazie YM, Movilla N, Ischenko I, Hayman MJ. The phospho-tyrosine phosphatase SHP2 is a critical mediator of transformationinduced by the oncogenic fibroblast growth factor receptor 3. Oncogene 2003; 22: 6909-18.
70. Ji H, Zhao X, Yuza Y, Shimamura T, Li D, Protopopov A, et al. Epidermal growth factor receptor variant III mutations in lungtumorigenesis and sensitivity to tyrosine kinase inhibitors. ProcNatl Acad Sci USA 2006; 103: 7817-22.
71. Zhan Y, Counelis GJ, O'Rourke DM. The protein tyrosinephosphatase SHP-2 is required for EGFRvIII oncogenic transfor-mation in human glioblastoma cells. Exp Cell Res 2009; 315:2343-57.
72. Voena C, Conte C, Ambrogio C, Boeri Erba E, Boccalatte F, Mohammed S, et al. The tyrosine phosphatase Shp2 interacts withNPM-ALK and regulates anaplastic lymphoma cell growth andmigration. Cancer Res 2007; 67: 4278-86.
73. Hatakeyama M. Oncogenic mechanisms of the Helicobacter pyloriCagA protein. Nat Rev Cancer 2004; 4: 688-94.
74. Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, et al. Mutations in PTPN11, encoding the proteintyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 2001; 29: 465-8.
75. Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, et al. Somatic mutations in PTPN11 in juvenile myelomonocyticleukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 2003; 34: 148-50.
76. Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, et al. Activating mutations of the noonan syndrome-associatedSHP2/PTPN11 gene in human solid tumors and adult acutemyelogenous leukemia. Cancer Res 2004; 64: 8816-20.
77. Loh ML, Reynolds MG, Vattikuti S, Gerbing RB, Alonzo TA, Carlson E, et al. PTPN11 mutations in pediatric patients with acutemyeloid leukemia: results from the Children's Cancer Group. Leukemia 2004; 18: 1831-4.
78. Chan RJ, Leedy MB, Munugalavadla V, Voorhorst CS, Li Y, Yu M, et al. Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulatingfactor. Blood 2005; 105: 3737-42.
79. Schubbert S, Lieuw K, Rowe SL, Lee CM, Li X, Loh ML, et al. Functional analysis of leukemia-associated PTPN11 mutations inprimary hematopoietic cells. Blood 2005; 106: 311-7.
80. Mohi MG, Williams IR, Dearolf CR, Chan G, Kutok JL, Cohen S, et al. Prognostic, therapeutic, and mechanistic implications of amouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell 2005; 7: 179-91.
81. Ren Y, Chen Z, Chen L, Woods NT, Reuther GW, Cheng JQ, et al. Shp2E76K mutant confers cytokine-independent survival of TF-1myeloid cells by up-regulating Bcl-XL. J Biol Chem 2007; 282:36463-73.
82. Chan G, Kalaitzidis D, Usenko T, Kutok JL, Yang W, Mohi MG, et al. Leukemogenic Ptpn11 causes fatal myeloproliferative disordervia cell-autonomous effects on multiple stages of hematopoiesis. Blood 2009; 113: 4414-24.
83. Chen L, Sung SS, Yip ML, Lawrence HR, Ren Y, Guida WC, et al. Discovery of a novel shp2 protein tyrosine phosphatase inhibitor.Mol Pharmacol 2006; 70: 562-70.
84. Zhao XT, Qian YK, Chan AW, Madhavan R, Peng HB. Regulationof ACh receptor clustering by the tyrosine phosphatase Shp2. Dev Neurobiol 2007; 67: 1789-801.
85. Qian YK, Chan AW, Madhavan R, Peng HB. The function of Shp2tyrosine phosphatase in the dispersal of acetylcholine receptorclusters. BMC Neurosci 2008; 9: 70.
86. Chatterjee PK, Al Abed Y, Sherry B, Metz CN. Cholinergic ago-nists regulate JAK2/STAT3 signaling to suppress endothelial cellactivation. Am J Physiol Cell Physiol 2009; 297(5): C1294-306.
87. Noren-Muller A, Reis-Correa I Jr, Prinz H, Rosenbaum C, Saxena K, Schwalbe HJ, et al. Discovery of protein phosphatase inhibitorclasses by biology-oriented synthesis. Proc Natl Acad Sci USA 2006; 103: 10606-11.
88. Geronikaki A, Eleftheriou P, Vicini P, Alam I, Dixit A, Saxena AK. 2-Thiazolylimino/heteroarylimino-5-arylidene-4-thiazoli-dinones as new agents with SHP-2 inhibitory action. J Med Chem 2008; 51: 5221-8.
89. Yu WM, Guvench O, Mackerell AD, Qu CK. Identification ofsmall molecular weight inhibitors of Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) via in silico databasescreening combined with experimental assay. J Med Chem 2008;51: 7396-404.
90. Gobert RP, van den Eijnden M, Szyndralewiez C, Jorand-Lebrun C, Swinnen D, Chen L, et al. GLEPP1/protein-tyrosine phos-phatase phi inhibitors block chemotaxis in vitro and in vivo andimprove murine ulcerative colitis. J Biol Chem 2009; 284: 11385-95.
91. Dawson MI, Xia Z, Jiang T, Ye M, Fontana JA, Farhana L, et al. Adamantyl-substituted retinoid-derived molecules that interact withthe orphan nuclear receptor small heterodimer partner: effects ofreplacing the 1-adamantyl or hydroxyl group on inhibition ofcancer cell growth, induction of cancer cell apoptosis, andinhibition of SRC homology 2 domain-containing protein tyrosinephosphatase-2 activity. J Med Chem 2008; 51: 5650-62.
92. Schaeper U, Gehring NH, Fuchs KP, Sachs M, Kempkes B, Birchmeier W. Coupling of Gab1 to c-Met, Grb2, and Shp2mediates biological responses. J Cell Biol 2000; 149: 1419-32.
93. Maroun CR, Naujokas MA, Holgado-Madruga M, Wong AJ, Park M. The tyrosine phosphatase SHP-2 is required for sustainedactivation of extracellular signal-regulated kinase and epithelialmorphogenesis downstream from the met receptor tyrosine kinase. Mol Cell Biol 2000; 20: 8513-25.
94. Bjorge JD, Pang A, Fujita DJ. Identification of protein-tyrosinephosphatase 1B as the major tyrosine phosphatase activity capableof dephosphorylating and activating c-Src in several human breastcancer cell lines. J Biol Chem 2000; 275: 41439-46.
95. Arias-Romero LE, Saha S, Villamar-Cruz O, Yip SC, Ethier SP, Zhang ZY, et al. Activation of Src by protein tyrosine phosphatase1B Is required for ErbB2 transformation of human breast epithelialcells. Cancer Res 2009; 69: 4582-8.
96. Zhu S, Bjorge JD, Fujita DJ. PTP1B contributes to the oncogenicproperties of colon cancer cells through Src activation. Cancer Res 2007; 67: 10129-37.
97. Dube N, Cheng A, Tremblay ML. The role of protein tyrosinephosphatase 1B in Ras signaling. Proc Natl Acad Sci USA 2004;101: 1834-9.
98. Zhang Z, Lin SY, Neel BG, Haimovich B. Phosphorylated alpha-actinin and protein-tyrosine phosphatase 1B coregulate thedisassembly of the focal adhesion kinase x Src complex andpromote cell migration. J Biol Chem 2006; 281: 1746-54.
99. Wiener JR, Hurteau JA, Kerns BJ, Whitaker RS, Conaway MR, Berchuck A, et al. Overexpression of the tyrosine phosphatasePTP1B is associated with human ovarian carcinomas. Am J ObstetGynecol 1994; 170: 1177-83.
100. Wiener JR, Kerns BJ, Harvey EL, Conaway MR, Iglehart JD, Berchuck A, et al. Overexpression of the protein tyrosine phos-phatase PTP1B in human breast cancer: association with p185c-erbB-2 protein expression. J Natl Cancer Inst 1994; 86: 372-8.
101. Bentires-Alj M, Neel BG. Protein-tyrosine phosphatase 1B isrequired for HER2/Neu-induced breast cancer. Cancer Res 2007;67: 2420-4.
102. Julien SG, Dube N, Read M, Penney J, Paquet M, Han Y, et al. Protein tyrosine phosphatase 1B deficiency or inhibition delaysErbB2-induced mammary tumorigenesis and protects from lungmetastasis. Nat Genet 2007; 39: 338-46.
103. Dube N, Bourdeau A, Heinonen KM, Cheng A, Loy AL, Tremblay ML. Genetic ablation of protein tyrosine phosphatase 1B accele-rates lymphomagenesis of p53-null mice through the regulation of B-cell development. Cancer Res 2005; 65: 10088-95.
104. Lee SY, Liang F, Guo XL, Xie L, Cahill SM, Blumenstein M, et al. Design, construction, and intracellular activation of an intramole-cularly self-silenced signal transduction inhibitor. Angew Chem IntEd Engl 2005; 44: 4242-4.
105. Boutselis IG, Yu X, Zhang ZY, Borch RF. Synthesis and cell-basedactivity of a potent and selective protein tyrosine phosphatase 1Binhibitor prodrug. J Med Chem 2007; 50: 856-64.
106. Han Y, Belley M, Bayly CI, Colucci J, Dufresne C, Giroux A, et al. Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro) methyl]phosphonic acid, a potent and orally active small molecule PTP1Binhibitor. Bioorg Med Chem Lett 2008; 18: 3200-5.
107. Erbe DV, Wang S, Zhang YL, Harding K, Kung L, Tam M, et al. Ertiprotafib improves glycemic control and lowers lipids viamultiple mechanisms. Mol Pharmacol 2005; 67: 69-77.
108. Lantz KA, Hart SG, Planey SL, Roitman MF, Ruiz-White IA, Wolfe HR, et al. Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring) 2010; (in press).
109. Rao MN, Shinnar AE, Noecker LA, Chao TL, Feibush B, Snyder B, et al. Aminosterols from the dogfish shark Squalus acanthias. JNat Prod 2000; 63: 631-5.
110. Stephens BJ, Han H, Gokhale V, Von Hoff DD. PRL phosphatasesas potential molecular targets in cancer. Mol Cancer Ther 2005; 4:1653-61.
111. Zeng Q, Si X, Horstmann H, Xu Y, Hong W, Pallen CJ. Prenylation-dependent association of protein-tyrosine phosphatasesPRL-1, -2, and -3 with the plasma membrane and the earlyendosome. J Biol Chem 2000; 275: 21444-52.
112. Saha S, Bardelli A, Buckhaults P, Velculescu VE, Rago C, St Croix B, et al. A phosphatase associated with metastasis of colorectalcancer. Science 2001; 294: 1343-6.
113. Bardelli A, Saha S, Sager JA, Romans KE, Xin B, Markowitz SD, et al. PRL-3 expression in metastatic cancers. Clin Cancer Res 2003; 9: 5607-15.
114. Peng L, Ning J, Meng L, Shou C. The association of the expressionlevel of protein tyrosine phosphatase PRL-3 protein with livermetastasis and prognosis of patients with colorectal cancer. J Cancer Res Clin Oncol 2004; 130: 521-6.
115. Rouleau C, Roy A, St Martin T, Dufault MR, Boutin P, Liu D, et al. Protein tyrosine phosphatase PRL-3 in malignant cells andendothelial cells: expression and function. Mol Cancer Ther 2006;5: 219-29.
116. Wang L, Peng L, Dong B, Kong L, Meng L, Yan L, et al. Overexpression of phosphatase of regenerating liver-3 in breastcancer: association with a poor clinical outcome. Ann Oncol 2006;17: 1517-22.
117. Miskad UA, Semba S, Kato H, Yokozaki H. Expression of PRL-3phosphatase in human gastric carcinomas: close correlation withinvasion and metastasis. Pathobiology 2004; 71: 176-84.
118. Zhao WB, Li Y, Liu X, Zhang LY, Wang X. Evaluation of PRL-3expression, and its correlation with angiogenesis and invasion inhepatocellular carcinoma. Int J Mol Med 2008; 22: 187-92.
119. Ren T, Jiang B, Xing X, Dong B, Peng L, Meng L, et al. Prognostic significance of phosphatase of regenerating liver-3expression in ovarian cancer. Pathol Oncol Res 2009; 15(4): 555-60.
120. Dai N, Lu AP, Shou CC, Li JY. Expression of phosphataseregenerating liver 3 is an independent prognostic indicator forgastric cancer. World J Gastroenterol 2009; 15: 1499-505.
121. Fagerli UM, Holt RU, Holien T, Vaatsveen TK, Zhan F, Egeberg KW, et al. Over expression and involvement in migration by themetastasis-associated phosphatase PRL-3 in human myeloma cells. Blood 2008; 111: 806-15.
122. Zeng Q, Dong JM, Guo K, Li J, Tan HX, Koh V, et al. PRL-3 andPRL-1 promote cell migration, invasion, and metastasis. CancerRes 2003; 63: 2716-22.
123. Guo K, Li J, Tang JP, Koh V, Gan BQ, Zeng Q. Catalytic domainof PRL-3 plays an essential role in tumor metastasis: formation ofPRL-3 tumors inside the blood vessels. Cancer Biol Ther 2004; 3:945-51.
124. Fiordalisi JJ, Keller PJ, Cox AD. PRL tyrosine phosphatasesregulate rho family GTPases to promote invasion and motility. Cancer Res 2006; 66: 3153-61.
125. Wang H, Quah SY, Dong JM, Manser E, Tang JP, Zeng Q. PRL-3down-regulates PTEN expression and signals through PI3K topromote epithelial-mesenchymal transition. Cancer Res 2007; 67:2922-6.
126. Achiwa H, Lazo JS. PRL-1 tyrosine phosphatase regulates c-Srclevels, adherence, and invasion in human lung cancer cells. CancerRes 2007; 67: 643-50.
127. Luo Y, Liang F, Zhang ZY. PRL1 Promotes Cell Migration andInvasion by Increasing MMP2 and MMP9 Expression through Srcand ERK1/2 Pathways (dagger). Biochemistry 2009; 48: 1838-46.
128. Forte E, Orsatti L, Talamo F, Barbato G, De Francesco R, Tomei L. Ezrin is a specific and direct target of protein tyrosine phosphatasePRL-3. Biochim Biophys Acta 2008; 1783: 334-44.
129. Kozlov G, Cheng J, Ziomek E, Banville D, Gehring K, Ekiel I. Structural insights into molecular function of the metastasis-associated phosphatase PRL-3. J Biol Chem 2004; 279: 11882-9.
130. Kim KA, Song JS, Jee J, Sheen MR, Lee C, Lee TG, et al. Structure of human PRL-3, the phosphatase associated with cancermetastasis. FEBS Lett 2004; 565: 181-7.
131. Jeong DG, Kim SJ, Kim JH, Son JH, Park MR, Lim SM, et al. Trimeric structure of PRL-1 phosphatase reveals an active enzymeconformation and regulation mechanisms. J Mol Biol 2005; 345:401-13.
132. Daouti S, Li WH, Qian H, Huang KS, Holmgren J, Levin W, et al. A selective phosphatase of regenerating liver phosphatase inhibitorsuppresses tumor cell anchorage-independent growth by a novelmechanism involving p130Cas cleavage. Cancer Res 2008; 68:1162-9.
133. Choi SK, Oh HM, Lee SK, Jeong DG, Ryu SE, Son KH, et al. Biflavonoids inhibited phosphatase of regenerating liver-3 (PRL-3). Nat Prod Res 2006; 20: 341-6.
134. Park H, Jung SK, Jeong DG, Ryu SE, Kim SJ. Discovery of novelPRL-3 inhibitors based on the structure-based virtual screening. Bioorg Med Chem Lett 2008; 18: 2250-5.
135. Ahn JH, Kim SJ, Park WS, Cho SY, Ha JD, Kim SS, et al. Synthesis and biological evaluation of rhodanine derivatives asPRL-3 inhibitors. Bioorg Med Chem Lett 2006; 16: 2996-9.
136. Pathak MK, Dhawan D, Lindner DJ, Borden EC, Farver C, Yi T. Pentamidine is an inhibitor of PRL phosphatases with anticanceractivity. Mol Cancer Ther 2002; 1: 1255-64.
137. Wang L, Shen Y, Song R, Sun Y, Xu J, Xu Q. An anticancer effectof curcumin mediated by down-regulating prl-3 expression onhighly metastatic melanoma cells. Mol Pharmacol 2009; 76(6):1238-45.
138. Visintin R, Craig K, Hwang ES, Prinz S, Tyers M, Amon A. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Mol Cell 1998; 2: 709-18.
139. Mailand N, Lukas C, Kaiser BK, Jackson PK, Bartek J, Lukas J. Deregulated human Cdc14A phosphatase disrupts centrosomeseparation and chromosome segregation. Nat Cell Biol 2002; 4:317-22.
140. Paulsen MT, Starks AM, Derheimer FA, Hanasoge S, Li L, Dixon JE, et al. The p53-targeting human phosphatase hCdc14A interactswith the Cdk1/cyclin B complex and is differentially expressed inhuman cancers. Mol Cancer 2006; 5: 25.
141. Esteban V, Vazquez-Novelle MD, Calvo E, Bueno A, Sacristan MP. Human Cdc14A reverses CDK1 phosphorylation of Cdc25Aon serines 115 and 320. Cell Cycle 2006; 5: 2894-8.
142. Lanzetti L, Margaria V, Melander F, Virgili L, Lee MH, Bartek J, et al. Regulation of the Rab5 GTPase-activating protein RN-tre bythe dual specificity phosphatase Cdc14A in human cells. J BiolChem 2007; 282: 15258-70.
143. Gray CH, Good VM, Tonks NK, Barford D. The structure of thecell cycle protein Cdc14 reveals a proline-directed proteinphosphatase. EMBO J 2003; 22: 3524-35.
144. Souza AC, Azoubel S, Queiroz KC, Peppelenbosch MP, Ferreira CV. From immune response to cancer: a spot on the low molecularweight protein tyrosine phosphatase. Cell Mol Life Sci 2009; 66:1140-53.
145. Cirri P, Fiaschi T, Chiarugi P, Camici G, Manao G, Raugei G, et al. The molecular basis of the differing kinetic behavior of the two lowmolecular mass phosphotyrosine protein phosphatase isoforms. JBiol Chem 1996; 271: 2604-7.
146. Malentacchi F, Marzocchini R, Gelmini S, Orlando C, Serio M, Ramponi G, et al. Up-regulated expression of low molecularweight protein tyrosine phosphatases in different human cancers. Biochem Biophys Res Commun 2005; 334: 875-83.
147. Miranda MA, Okamoto AK, Ferreira CV, Silva TL, Granjeiro JM, Aoyama H. Differential effects of flavonoids on bovine kidney lowmolecular mass protein tyrosine phosphatase. J Enzyme Inhib MedChem 2006; 21: 419-25.
148. Bispo de Jesus M, Zambuzzi WF, Ruela de Sousa RR, Areche C, Santos de Souza AC, Aoyama H, et al. Ferruginol suppressessurvival signaling pathways in androgen-independent human prostate cancer cells. Biochimie 2008; 90: 843-54.
149. Forghieri M, Laggner C, Paoli P, Langer T, Manao G, Camici G, et al. Synthesis, activity and molecular modeling of a new series ofchromones as low molecular weight protein tyrosine phosphataseinhibitors. Bioorg Med Chem 2009; 17: 2658-72.
150. Maccari R, Ottana R, Ciurleo R, Paoli P, Manao G, Camici G, et al. Structure-based optimization of benzoic acids as inhibitors ofprotein tyrosine phosphatase 1B and low molecular weight proteintyrosine phosphatase. ChemMedChem 2009; 4: 957-62.
151. Boutros R, Lobjois V, Ducommun B. CDC25 phosphatases incancer cells: key players? Good targets? Nat Rev Cancer 2007; 7:495-507.
152. Ray D, Terao Y, Fuhrken PG, Ma ZQ, DeMayo FJ, Christov K, et al. Deregulated CDC25A expression promotes mammary tumori-genesis with genomic instability. Cancer Res 2007; 67: 984-91.
153. Ray D, Terao Y, Nimbalkar D, Hirai H, Osmundson EC, Zou X, et al. Hemizygous disruption of Cdc25A inhibits cellular transfor-mation and mammary tumorigenesis in mice. Cancer Res 2007; 67:6605-11.
154. Wei S, Chen X, Rocha K, Epling-Burnette PK, Djeu JY, Liu Q, et al. A critical role for phosphatase haplodeficiency in the selectivesuppression of deletion 5q MDS by lenalidomide. Proc Natl AcadSci USA 2009; 106: 12974-9.
155. Brezak MC, Valette A, Quaranta M, Contour-Galcera MO, Jullien D, Lavergne O, et al. IRC-083864, a novel bis quinone inhibitor ofCDC25 phosphatases active against human cancer cells. Int JCancer 2009; 124: 1449-56.
156. Brezak MC, Quaranta M, Mondesert O, Galcera MO, Lavergne O, Alby F, et al. A novel synthetic inhibitor of CDC25 phosphatases:BN82002. Cancer Res 2004; 64: 3320-5.
157. Brezak MC, Quaranta M, Contour-Galcera MO, Lavergne O, Mondesert O, Auvray P, et al. Inhibition of human tumor cellgrowth in vivo by an orally bioavailable inhibitor of CDC25 phosphatases. Mol Cancer Ther 2005; 4: 1378-87.
158. Brezak MC, Kasprzyk PG, Galcera MO, Lavergne O, Prevost GP. CDC25 inhibitors as anticancer agents are moving forward.Anticancer Agents Med Chem 2008; 8: 857-62.
159. Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK, et al. Eyaprotein phosphatase activity regulates Six1-Dach-Eya transcrip-tional effects in mammalian organogenesis. Nature 2003; 426: 247-54.
160. Tootle TL, Silver SJ, Davies EL, Newman V, Latek RR, Mills IA, et al. The transcription factor Eyes absent is a protein tyrosinephosphatase. Nature 2003; 426: 299-302.
161. Rayapureddi JP, Kattamuri C, Steinmetz BD, Frankfort BJ, Ostrin EJ, Mardon G, et al. Eyes absent represents a class of proteintyrosine phosphatases. Nature 2003; 426: 295-8.
162. Zhang L, Yang N, Huang J, Buckanovich RJ, Liang S, Barchetti A, et al. Transcriptional coactivator Drosophila eyes absenthomologue 2 is up-regulated in epithelial ovarian cancer andpromotes tumor growth. Cancer Res 2005; 65: 925-32.
163. Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov 2002; 1: 727-30.