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The Role of TCPTP in Cancer

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Book cover Protein Tyrosine Phosphatases in Cancer

Abstract

Human T cell protein tyrosine phosphatase (TCPTP; encoded by PTPN2) is a ubiquitous non-transmembrane tyrosine-specific phosphatase. TCPTP substrates include protein tyrosine kinases (PTKs) such as the epidermal growth factor receptor, Janus activated kinase (JAK) and c-Src and PTK substrates such as STAT3 and STAT5. TCPTP deficiency can enhance oncogenic tyrosine phosphorylation-dependent signalling to promote growth and survival, perturb cell cycle checkpoints and to promote tumorigenicity in vitro and in vivo. Recent studies have identified TCPTP as a bona fide tumour suppressor being deleted in TLX1 overexpressing T cell acute lymphoblastic leukemias (T-ALLs) to promote cytokine signalling and to sensitise cells to transformation by oncogenic PTKs. TCPTP has also been identified as potential tumour suppressor in solid malignancies, in particular in breast cancer, promoting STAT3 signalling and tumorigenicity. This chapter will explore how perturbations in TCPTP regulation and function may contribute to the development of cancer, focusing in particular on TCPTP’s roles in T-ALL and breast cancer.

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Abbreviations

ABC:

Activated-B-cell

AMPK:

AMP-activated protein kinase

c-Met:

HGF receptor

DLBCL:

Diffuse large B-cell lymphomas

EGF:

Epidermal growth factor

EGFR:

EGF receptor

ER:

Oestrogen receptor

GAB2:

Growth factor receptor-bound protein 2

GCB:

Germinal centre B-cell

HCC:

Hepatocellular carcinoma

HGF:

Hepatocyte growth factor

IFN:

Interferon

IL:

Interleukin

IR:

Insulin receptor

JAK:

(Janus-activated kinase)

MAPK:

Mitogen-activated protein kinase

NLS:

Nuclear localisation signal

NPC:

Nuclear pore complex

PDGFR:

Platelet-derived growth factor receptor

PI3K:

Phosphatidylinositol 3-kinase

PTK:

Protein tyrosine kinase

PTP:

Protein tyrosine phosphatase

PTP1B:

Protein tyrosine phosphatase 1B

SFK:

Src family kinase

SHP-2:

Src homology phosphatase-2

SOCS3:

Suppressor of cytokine signaling 3

STAT:

Signal transducer and activator of transcription

T-ALL:

T cell acute lymphoblastic leukemia

TCPTP:

T cell PTP

References

  1. Tonks NK. Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol. 2006;7:833–46.

    Article  CAS  PubMed  Google Scholar 

  2. Tiganis T, Bennett AM. Protein tyrosine phosphatase function: the substrate perspective. Biochem J. 2007;402:1–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ostman A, Hellberg C, Bohmer FD. Protein-tyrosine phosphatases and cancer. Nat Rev Cancer. 2006;6:307–20.

    Article  PubMed  CAS  Google Scholar 

  4. Julien SG, Dube N, Hardy S, Tremblay ML. Inside the human cancer tyrosine phosphatome. Nat Rev Cancer. 2011;11:35–49.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang SQ, Yang W, Kontaridis MI, Bivona TG, Wen G, Araki T, Luo J, Thompson JA, Schraven BL, Philips MR, et al. Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol Cell. 2004;13:341–55.

    Article  PubMed  Google Scholar 

  6. Mohi MG, Williams IR, Dearolf CR, Chan G, Kutok JL, Cohen S, Morgan K, Boulton C, Shigematsu H, Keilhack H, et al. Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell. 2005;7:179–91.

    Article  CAS  PubMed  Google Scholar 

  7. Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, et al. Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res. 2004;64:8816–20.

    Article  CAS  PubMed  Google Scholar 

  8. Bentires-Alj M, Gil SG, Chan R, Wang ZC, Wang Y, Imanaka N, Harris LN, Richardson A, Neel BG, Gu H. A role for the scaffolding adapter GAB2 in breast cancer. Nat Med. 2006;12:114–21.

    Article  CAS  PubMed  Google Scholar 

  9. Aceto N, Sausgruber N, Brinkhaus H, Gaidatzis D, Martiny-Baron G, Mazzarol G, Confalonieri S, Quarto M, Hu G, Balwierz PJ, et al. Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop. Nat Med. 2012;18:529–37.

    Article  CAS  PubMed  Google Scholar 

  10. Bjorge JD, Pang A, Fujita DJ. Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J Biol Chem. 2000;275:41439–46.

    Article  CAS  PubMed  Google Scholar 

  11. Wiener JR, Kerns BJ, Harvey EL, Conaway MR, Iglehart JD, Berchuck A, Bast Jr RC. Overexpression of the protein tyrosine phosphatase PTP1B in human breast cancer: association with p185c-erbB-2 protein expression. J Natl Cancer Inst. 1994;86:372–8.

    Article  CAS  PubMed  Google Scholar 

  12. Courjal F, Cuny M, Rodriguez C, Louason G, Speiser P, Katsaros D, Tanner MM, Zeillinger R, Theillet C. DNA amplifications at 20q13 and MDM2 define distinct subsets of evolved breast and ovarian tumours. Br J Cancer. 1996;74:1984–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bentires-Alj M, Neel BG. Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Cancer Res. 2007;67:2420–4.

    Article  CAS  PubMed  Google Scholar 

  14. Julien SG, Dube N, Read M, Penney J, Paquet M, Han Y, Kennedy BP, Muller WJ, Tremblay ML. Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat Genet. 2007;39:338–46.

    Article  CAS  PubMed  Google Scholar 

  15. Tonks NK, Muthuswamy SK. A brake becomes an accelerator: PTP1B—a new therapeutic target for breast cancer. Cancer Cell. 2007;11:214–6.

    Article  CAS  PubMed  Google Scholar 

  16. Ruivenkamp CA, van Wezel T, Zanon C, Stassen AP, Vlcek C, Csikos T, Klous AM, Tripodis N, Perrakis A, Boerrigter L, et al. Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers. Nat Genet. 2002;31:295–300.

    Article  CAS  PubMed  Google Scholar 

  17. Ruivenkamp C, Hermsen M, Postma C, Klous A, Baak J, Meijer G, Demant P. LOH of PTPRJ occurs early in colorectal cancer and is associated with chromosomal loss of 18q12-21. Oncogene. 2003;22:3472–4.

    Article  CAS  PubMed  Google Scholar 

  18. Wang Z, Shen D, Parsons DW, Bardelli A, Sager J, Szabo S, Ptak J, Silliman N, Peters BA, van der Heijden MS, et al. Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science. 2004;304:1164–6.

    Article  CAS  PubMed  Google Scholar 

  19. Motiwala T, Kutay H, Ghoshal K, Bai S, Seimiya H, Tsuruo T, Suster S, Morrison C, Jacob ST. Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer. Proc Natl Acad Sci U S A. 2004;101:13844–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Motiwala T, Ghoshal K, Das A, Majumder S, Weichenhan D, Wu YZ, Holman K, James SJ, Jacob ST, Plass C. Suppression of the protein tyrosine phosphatase receptor type O gene (PTPRO) by methylation in hepatocellular carcinomas. Oncogene. 2003;22:6319–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yu M, Lin G, Arshadi N, Kalatskaya I, Xue B, Haider S, Nguyen F, Boutros PC, Elson A, Muthuswamy LB, et al. Expression profiling during mammary epithelial cell three-dimensional morphogenesis identifies PTPRO as a novel regulator of morphogenesis and ErbB2-mediated transformation. Mol Cell Biol. 2012;32:3913–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ramaswamy B, Majumder S, Roy S, Ghoshal K, Kutay H, Datta J, Younes M, Shapiro CL, Motiwala T, Jacob ST. Estrogen-mediated suppression of the gene encoding protein tyrosine phosphatase PTPRO in human breast cancer: mechanism and role in tamoxifen sensitivity. Mol Endocrinol. 2009;23:176–87.

    Article  CAS  PubMed  Google Scholar 

  23. Sun T, Aceto N, Meerbrey KL, Kessler JD, Zhou C, Migliaccio I, Nguyen DX, Pavlova NN, Botero M, Huang J, et al. Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase. Cell. 2011;144:703–18.

    Article  CAS  PubMed  Google Scholar 

  24. Tiganis T. PTP1B and TCPTP—nonredundant phosphatases in insulin signaling and glucose homeostasis. FEBS J. 2012;280(2):445–58.

    Article  PubMed  CAS  Google Scholar 

  25. Cool DE, Tonks NK, Charbonneau H, Walsh KA, Fischer EH, Krebs EG. cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family. Proc Natl Acad Sci U S A. 1989;86:5257–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. You-Ten KE, Muise ES, Itie A, Michaliszyn E, Wagner J, Jothy S, Lapp WS, Tremblay ML. Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice. J Exp Med. 1997;186:683–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wiede F, Shields BJ, Chew SH, Kyparissoudis K, van Vliet C, Galic S, Tremblay ML, Russell SM, Godfrey DI, Tiganis T. T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice. J Clin Invest. 2011;121:4758–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kleppe M, Lahortiga I, El Chaar T, De Keersmaecker K, Mentens N, Graux C, Van Roosbroeck K, Ferrando AA, Langerak AW, Meijerink JP, et al. Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nat Genet. 2010;42:530–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shields BJ, Wiede F, Gurzov EN, Wee K, Hauser C, Zhu HJ, Molloy TJ, O’Toole SA, Daly RJ, Sutherland RL, et al. TCPTP regulates SFK and STAT3 signalling and is lost in triple negative breast cancers. Mol Cell Biol. 2013;33:557–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mosinger Jr B, Tillmann U, Westphal H, Tremblay ML. Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase. Proc Natl Acad Sci U S A. 1992;89:499–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lorenzen JA, Dadabay CY, Fischer EH. COOH-Terminal sequence motifs target the T-cell protein tyrosine phosphatase to the ER and nucleus. J Cell Biol. 1995;131:631–43.

    Article  CAS  PubMed  Google Scholar 

  32. Tiganis T, Flint AJ, Adam SA, Tonks NK. Association of the T-cell protein tyrosine phosphatase with nuclear import factor p97. J Biol Chem. 1997;272:21548–57.

    Article  CAS  PubMed  Google Scholar 

  33. Gupta V, Swarup G. Evidence for a role of transmembrane protein p25 in localization of protein tyrosine phosphatase TC48 to the ER. J Cell Sci. 2006;119:1703–14.

    Article  CAS  PubMed  Google Scholar 

  34. Lam MH, Michell BJ, Fodero-Tavoletti MT, Kemp BE, Tonks NK, Tiganis T. Cellular stress regulates the nucleocytoplasmic distribution of the protein tyrosine phosphatase TCPTP. J Biol Chem. 2001;276:37700–7.

    Article  CAS  PubMed  Google Scholar 

  35. Tiganis T, Bennett AM, Ravichandran KS, Tonks NK. Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase. Mol Cell Biol. 1998;18:1622–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. van Vliet C, Bukczynska PE, Puryer MA, Sadek CM, Shields BJ, Tremblay ML, Tiganis T. Selective regulation of tumor necrosis factor-induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase. Nat Immunol. 2005;6:253–60.

    Article  PubMed  CAS  Google Scholar 

  37. Galic S, Klingler-Hoffmann M, Fodero-Tavoletti MT, Puryer MA, Meng TC, Tonks NK, Tiganis T. Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP. Mol Cell Biol. 2003;23:2096–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tiganis T, Kemp BE, Tonks NK. The protein tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signalling. J Biol Chem. 1999;274:27768–75.

    Article  CAS  PubMed  Google Scholar 

  39. Mattila E, Pellinen T, Nevo J, Vuoriluoto K, Arjonen A, Ivaska J. Negative regulation of EGFR signalling through integrin-alpha1beta1-mediated activation of protein tyrosine phosphatase TCPTP. Nat Cell Biol. 2005;7:78–85.

    Article  CAS  PubMed  Google Scholar 

  40. Luo Z, Saha AK, Xiang X, Ruderman NB. AMPK, the metabolic syndrome and cancer. Trends Pharmacol Sci. 2005;26:69–76.

    Article  CAS  PubMed  Google Scholar 

  41. Talamonti MS, Roh MS, Curley SA, Gallick GE. Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer. J Clin Invest. 1993;91:53–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cartwright CA, Coad CA, Egbert BM. Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative colitis. J Clin Invest. 1994;93:509–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Irby RB, Mao W, Coppola D, Kang J, Loubeau JM, Trudeau W, Karl R, Fujita DJ, Jove R, Yeatman TJ. Activating SRC mutation in a subset of advanced human colon cancers. Nat Genet. 1999;21:187–90.

    Article  CAS  PubMed  Google Scholar 

  44. Yeatman TJ. A renaissance for SRC. Nat Rev Cancer. 2004;4:470–80.

    Article  CAS  PubMed  Google Scholar 

  45. Boudeau J, Sapkota G, Alessi DR. LKB1, a protein kinase regulating cell proliferation and polarity. FEBS Lett. 2003;546:159–65.

    Article  CAS  PubMed  Google Scholar 

  46. Tiainen M, Vaahtomeri K, Ylikorkala A, Makela TP. Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1). Hum Mol Genet. 2002;11:1497–504.

    Article  CAS  PubMed  Google Scholar 

  47. Liu W, Monahan KB, Pfefferle AD, Shimamura T, Sorrentino J, Chan KT, Roadcap DW, Ollila DW, Thomas NE, Castrillon DH, et al. LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma. Cancer Cell. 2012;21:751–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Klingler-Hoffmann M, Fodero-Tavoletti MT, Mishima K, Narita Y, Cavenee WK, Furnari FB, Huang HJ, Tiganis T. The protein tyrosine phosphatase TCPTP suppresses the tumorigenicity of glioblastoma cells expressing a mutant epidermal growth factor receptor. J Biol Chem. 2001;276:46313–8.

    Article  CAS  PubMed  Google Scholar 

  49. Persson C, Savenhed C, Bourdeau A, Tremblay ML, Markova B, Bohmer FD, Haj FG, Neel BG, Elson A, Heldin CH, et al. Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase. Mol Cell Biol. 2004;24:2190–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sangwan V, Paliouras GN, Abella JV, Dube N, Monast A, Tremblay ML, Park M. Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase. J Biol Chem. 2008;283:34374–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Shields BJ, Hauser C, Bukczynska PE, Court NW, Tiganis T. DNA replication stalling attenuates tyrosine kinase signaling to suppress S phase progression. Cancer Cell. 2008;14:166–79.

    Article  CAS  PubMed  Google Scholar 

  52. Simoncic PD, Lee-Loy A, Barber DL, Tremblay ML, McGlade CJ. The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr Biol. 2002;12:446–53.

    Article  CAS  PubMed  Google Scholar 

  53. ten Hoeve J, Ibarra-Sanchez MJ, Fu Y, Zhu W, Tremblay M, David M, Shuai K. Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002;22:5662–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Aoki N, Matsuda T. A nuclear protein tyrosine phosphatase TC-PTP is a potential negative regulator of the PRL-mediated signaling pathway: dephosphorylation and deactivation of signal transducer and activator of transcription 5a and 5b by TC-PTP in nucleus. Mol Endocrinol. 2002;16:58–69.

    Article  CAS  PubMed  Google Scholar 

  55. Yamamoto T, Sekine Y, Kashima K, Kubota A, Sato N, Aoki N, Matsuda T. The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Biochem Biophys Res Commun. 2002;297:811–7.

    Article  CAS  PubMed  Google Scholar 

  56. Lu X, Chen J, Sasmono RT, Hsi ED, Sarosiek KA, Tiganis T, Lossos IS. T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6. Mol Cell Biol. 2007;27:2166–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Fukushima A, Loh K, Galic S, Fam B, Shields B, Wiede F, Tremblay ML, Watt MJ, Andrikopoulos S, Tiganis T. T-cell protein tyrosine phosphatase attenuates STAT3 and insulin signaling in the liver to regulate gluconeogenesis. Diabetes. 2010;59:1906–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Loh K, Fukushima A, Zhang X, Galic S, Briggs D, Enriori PJ, Simonds S, Wiede F, Reichenbach A, Hauser C, et al. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance. Cell Metab. 2011;14:684–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9:798–809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yu H, Jove R. The STATs of cancer—new molecular targets come of age. Nat Rev Cancer. 2004;4:97–105.

    Article  CAS  PubMed  Google Scholar 

  61. Flint AJ, Tiganis T, Barford D, Tonks NK. Development of “substrate-trapping” mutants to identify physiological substrates of protein tyrosine phosphatases. Proc Natl Acad Sci U S A. 1997;94:1680–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Haj FG, Verveer PJ, Squire A, Neel BG, Bastiaens PI. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science. 2002;295:1708–11.

    Article  CAS  PubMed  Google Scholar 

  63. Muppirala M, Gupta V, Swarup G. Tyrosine phosphorylation of a SNARE protein, syntaxin 17: implications for membrane trafficking in the early secretory pathway. Biochim Biophys Acta. 2012;1823:2109–19.

    Article  CAS  PubMed  Google Scholar 

  64. Mitra A, Kalayarasan S, Gupta V, Radha V. TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells. PLoS One. 2011;6, e23681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wiede F, Hui Chew S, van Vliet C, Poulton IJ, Kyparissoudis K, Sasmono T, Loh K, Tremblay ML, Godfrey DI, Sims NA, et al. Strain-dependent differences in bone development, myeloid hyperplasia, morbidity and mortality in Ptpn2-deficient mice. PLoS One. 2012;7, e36703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Loh K, Merry TL, Galic S, Wu BJ, Watt MJ, Zhang S, Zhang ZY, Neel BG, Tiganis T. T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice. Diabetologia. 2012;55:468–78.

    Article  CAS  PubMed  Google Scholar 

  67. Zee T, Settembre C, Levine RL, Karsenty G. T-cell protein tyrosine phosphatase regulates bone resorption and whole-body insulin sensitivity through its expression in osteoblasts. Mol Cell Biol. 2012;32:1080–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Heinonen KM, Nestel FP, Newell EW, Charette G, Seemayer TA, Tremblay ML, Lapp WS. T cell protein tyrosine phosphatase deletion results in progressive systemic inflammatory disease. Blood. 2004;103(9):3457–64.

    Article  CAS  PubMed  Google Scholar 

  69. Bourdeau A, Dube N, Heinonen KM, Theberge JF, Doody KM, Tremblay ML. TC-PTP-deficient bone marrow stromal cells fail to support normal B lymphopoiesis due to abnormal secretion of interferon-{gamma}. Blood. 2007;109:4220–8.

    Article  CAS  PubMed  Google Scholar 

  70. Bourdeau A, Trop S, Doody KM, Dumont DJ, Tremblay ML. Inhibition of T cell protein tyrosine phosphatase (TC-PTP) enhances IL-18-dependent hematopoietic stem cell expansion. Stem Cells. 2013;31(2):293–304.

    Google Scholar 

  71. Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature. 2001;411:355–65.

    Article  CAS  PubMed  Google Scholar 

  72. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012;12:89–103.

    Article  CAS  PubMed  Google Scholar 

  73. Burgess AW. EGFR family: structure physiology signalling and therapeutic targets. Growth Factors. 2008;26:263–74.

    Article  CAS  PubMed  Google Scholar 

  74. Bartek J, Lukas C, Lukas J. Checking on DNA damage in S phase. Nat Rev Mol Cell Biol. 2004;5:792–804.

    Article  CAS  PubMed  Google Scholar 

  75. Shields BJ, Tiganis T. Replication checkpoint control by a PTK/STAT3/cyclin D1 axis. Cell Cycle. 2009;8:223–30.

    Article  CAS  PubMed  Google Scholar 

  76. Young RM, Polsky A, Refaeli Y. TC-PTP is required for the maintenance of MYC-driven B-cell lymphomas. Blood. 2009;114:5016–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shimizu T, Miyakawa Y, Iwata S, Kuribara A, Tiganis T, Morimoto C, Ikeda Y, Kizaki M. A novel mechanism for imatinib mesylate (STI571) resistance in CML cell line KT-1: role of TC-PTP in modulating signals downstream from the BCR-ABL fusion protein. Exp Hematol. 2004;32:1057–63.

    Article  CAS  PubMed  Google Scholar 

  78. Kleppe M, Soulier J, Asnafi V, Mentens N, Hornakova T, Knoops L, Constantinescu S, Sigaux F, Meijerink JP, Vandenberghe P, et al. PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia. Blood. 2011;117:7090–8.

    Article  CAS  PubMed  Google Scholar 

  79. Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, Gupta S, Moore J, Wrobel MJ, Lerner J, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med. 2008;359:1995–2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lee CF, Ling ZQ, Zhao T, Fang SH, Chang WC, Lee SC, Lee KR. Genomic-wide analysis of lymphatic metastasis-associated genes in human hepatocellular carcinoma. World J Gastroenterol. 2009;15:356–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Aifantis I, Raetz E, Buonamici S. Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat Rev Immunol. 2008;8:380–90.

    Article  CAS  PubMed  Google Scholar 

  82. Van Vlierberghe P, Ferrando A. The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest. 2012;122:3398–406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 2002;1:75–87.

    Article  CAS  PubMed  Google Scholar 

  84. Goldberg JM, Silverman LB, Levy DE, Dalton VK, Gelber RD, Lehmann L, Cohen HJ, Sallan SE, Asselin BL. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J Clin Oncol. 2003;21:3616–22.

    Article  PubMed  Google Scholar 

  85. Oudot C, Auclerc MF, Levy V, Porcher R, Piguet C, Perel Y, Gandemer V, Debre M, Vermylen C, Pautard B, et al. Prognostic factors for leukemic induction failure in children with acute lymphoblastic leukemia and outcome after salvage therapy: the FRALLE 93 study. J Clin Oncol. 2008;26:1496–503.

    Article  CAS  PubMed  Google Scholar 

  86. Hebert J, Cayuela JM, Berkeley J, Sigaux F. Candidate tumor-suppressor genes MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from T- but not from B-cell lineage acute lymphoblastic leukemias. Blood. 1994;84:4038–44.

    CAS  PubMed  Google Scholar 

  87. Weng AP, Ferrando AA, Lee W, Morris JPT, Silverman LB, Sanchez-Irizarry C, Blacklow SC, Look AT, Aster JC. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306:269–71.

    Article  CAS  PubMed  Google Scholar 

  88. Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R, Vermeesch JR, Stul M, Dutta B, Boeckx N, et al. Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet. 2004;36:1084–9.

    Article  CAS  PubMed  Google Scholar 

  89. Asnafi V, Le Noir S, Lhermitte L, Gardin C, Legrand F, Vallantin X, Malfuson JV, Ifrah N, Dombret H, Macintyre E. JAK1 mutations are not frequent events in adult T-ALL: a GRAALL study. Br J Haematol. 2010;148:178–9.

    Article  PubMed  Google Scholar 

  90. Flex E, Petrangeli V, Stella L, Chiaretti S, Hornakova T, Knoops L, Ariola C, Fodale V, Clappier E, Paoloni F, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med. 2008;205:751–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Quintas-Cardama A, Kantarjian H, Cortes J. Imatinib and beyond—exploring the full potential of targeted therapy for CML. Nat Rev Clin Oncol. 2009;6:535–43.

    Article  CAS  PubMed  Google Scholar 

  92. Quintas-Cardama A, Tong W, Manshouri T, Vega F, Lennon PA, Cools J, Gilliland DG, Lee F, Cortes J, Kantarjian H, et al. Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia. 2008;22:1117–24.

    Article  CAS  PubMed  Google Scholar 

  93. Quintas-Cardama A, Kantarjian H, Cortes J, Verstovsek S. Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat Rev Drug Discov. 2011;10:127–40.

    Article  CAS  PubMed  Google Scholar 

  94. Hogquist KA, Baldwin TA, Jameson SC. Central tolerance: learning self-control in the thymus. Nat Rev Immunol. 2005;5:772–82.

    Article  CAS  PubMed  Google Scholar 

  95. Daniels MA, Teixeiro E, Gill J, Hausmann B, Roubaty D, Holmberg K, Werlen G, Hollander GA, Gascoigne NR, Palmer E. Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling. Nature. 2006;444:724–9.

    Article  CAS  PubMed  Google Scholar 

  96. Palmer E, Naeher D. Affinity threshold for thymic selection through a T-cell receptor-co-receptor zipper. Nat Rev Immunol. 2009;9:207–13.

    Article  CAS  PubMed  Google Scholar 

  97. Rakowski LA, Lehotzky EA, Chiang MY. Transient responses to NOTCH and TLX1/HOX11 inhibition in T-cell acute lymphoblastic leukemia/lymphoma. PLoS One. 2011;6, e16761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, et al. The TLX1 oncogene drives aneuploidy in T cell transformation. Nat Med. 2010;16:1321–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Owens BM, Hawley TS, Spain LM, Kerkel KA, Hawley RG. TLX1/HOX11-mediated disruption of primary thymocyte differentiation prior to the CD4 + CD8+ double-positive stage. Br J Haematol. 2006;132:216–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Reddy KB. Triple-negative breast cancers: an updated review on treatment options. Curr Oncol. 2011;18:e173–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yarden Y. Biology of HER2 and its importance in breast cancer. Oncology. 2001;61 Suppl 2:1–13.

    Article  CAS  PubMed  Google Scholar 

  102. Di Marco E, Pierce JH, Knicley CL, Di Fiore PP. Transformation of NIH 3T3 cells by overexpression of the normal coding sequence of the rat neu gene. Mol Cell Biol. 1990;10:3247–52.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Di Fiore PP, Pierce JH, Kraus MH, Segatto O, King CR, Aaronson SA. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987;237:178–82.

    Article  PubMed  Google Scholar 

  104. Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell. 1988;54:105–15.

    Article  CAS  PubMed  Google Scholar 

  105. Corkery B, Crown J, Clynes M, O’Donovan N. Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Ann Oncol. 2009;20(5):862–7.

    Article  CAS  PubMed  Google Scholar 

  106. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.

    Article  CAS  PubMed  Google Scholar 

  107. Muthuswamy SK, Li D, Lelievre S, Bissell MJ, Brugge JS. ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini. Nat Cell Biol. 2001;3:785–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Biscardi JS, Belsches AP, Parsons SJ. Characterization of human epidermal growth factor receptor and c-Src interactions in human breast tumor cells. Mol Carcinog. 1998;21:261–72.

    Article  CAS  PubMed  Google Scholar 

  109. Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH, Parsons SJ. c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function. J Biol Chem. 1999;274:8335–43.

    Article  CAS  PubMed  Google Scholar 

  110. Olayioye MA, Badache A, Daly JM, Hynes NE. An essential role for Src kinase in ErbB receptor signaling through the MAPK pathway. Exp Cell Res. 2001;267:81–7.

    Article  CAS  PubMed  Google Scholar 

  111. Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE. ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J Biol Chem. 1999;274:17209–18.

    Article  CAS  PubMed  Google Scholar 

  112. Dimri M, Naramura M, Duan L, Chen J, Ortega-Cava C, Chen G, Goswami R, Fernandes N, Gao Q, Dimri GP, et al. Modeling breast cancer-associated c-Src and EGFR overexpression in human MECs: c-Src and EGFR cooperatively promote aberrant three-dimensional acinar structure and invasive behavior. Cancer Res. 2007;67:4164–72.

    Article  CAS  PubMed  Google Scholar 

  113. Verbeek BS, Vroom TM, Adriaansen-Slot SS, Ottenhoff-Kalff AE, Geertzema JG, Hennipman A, Rijksen G. c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis. J Pathol. 1996;180:383–8.

    Article  CAS  PubMed  Google Scholar 

  114. Hsieh FC, Cheng G, Lin J. Evaluation of potential Stat3-regulated genes in human breast cancer. Biochem Biophys Res Commun. 2005;335:292–9.

    Article  CAS  PubMed  Google Scholar 

  115. Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel MA. Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. J Biol Chem. 1986;261:13754–9.

    CAS  PubMed  Google Scholar 

  116. Diaz N, Minton S, Cox C, Bowman T, Gritsko T, Garcia R, Eweis I, Wloch M, Livingston S, Seijo E, et al. Activation of stat3 in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression. Clin Cancer Res. 2006;12:20–8.

    Article  CAS  PubMed  Google Scholar 

  117. Wilson GR, Cramer A, Welman A, Knox F, Swindell R, Kawakatsu H, Clarke RB, Dive C, Bundred NJ. Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity. Br J Cancer. 2006;95:1410–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N, Slamon DJ. Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro. Breast Cancer Res Treat. 2007;105:319–26.

    Article  CAS  PubMed  Google Scholar 

  119. Finn RS. Targeting Src in breast cancer. Ann Oncol. 2008;19:1379–86.

    Article  CAS  PubMed  Google Scholar 

  120. Muthuswamy SK, Muller WJ. Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor. Oncogene. 1995;11:271–9.

    CAS  PubMed  Google Scholar 

  121. Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, Nam S, Eweis I, Diaz N, Sullivan D, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res. 2006;12:11–9.

    Article  CAS  PubMed  Google Scholar 

  122. Hochgrafe F, Zhang L, O’Toole SA, Browne BC, Pinese M, Porta Cubas A, Lehrbach GM, Croucher DR, Rickwood D, Boulghourjian A, et al. Tyrosine phosphorylation profiling reveals the signaling network characteristics of Basal breast cancer cells. Cancer Res. 2010;70:9391–401.

    Article  PubMed  CAS  Google Scholar 

  123. Alvarez JV, Febbo PG, Ramaswamy S, Loda M, Richardson A, Frank DA. Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors. Cancer Res. 2005;65:5054–62.

    Article  CAS  PubMed  Google Scholar 

  124. Chapman RS, Lourenco PC, Tonner E, Flint DJ, Selbert S, Takeda K, Akira S, Clarke AR, Watson CJ. Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev. 1999;13:2604–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Ling X, Arlinghaus RB. Knockdown of STAT3 expression by RNA interference inhibits the induction of breast tumors in immunocompetent mice. Cancer Res. 2005;65:2532–6.

    Article  CAS  PubMed  Google Scholar 

  126. Barbieri I, Quaglino E, Maritano D, Pannellini T, Riera L, Cavallo F, Forni G, Musiani P, Chiarle R, Poli V. Stat3 is required for anchorage-independent growth and metastasis but not for mammary tumor development downstream of the ErbB-2 oncogene. Mol Carcinog. 2010;49:114–20.

    CAS  PubMed  Google Scholar 

  127. Kritikou EA, Sharkey A, Abell K, Came PJ, Anderson E, Clarkson RW, Watson CJ. A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland. Development. 2003;130:3459–68.

    Article  CAS  PubMed  Google Scholar 

  128. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003;374:1–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Garcia R, Bowman TL, Niu G, Yu H, Minton S, Muro-Cacho CA, Cox CE, Falcone R, Fairclough R, Parsons S, et al. Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene. 2001;20:2499–513.

    Article  CAS  PubMed  Google Scholar 

  130. Sutherland KD, Lindeman GJ, Choong DY, Wittlin S, Brentzell L, Phillips W, Campbell IG, Visvader JE. Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene. 2004;23:7726–33.

    Article  CAS  PubMed  Google Scholar 

  131. Selander KS, Li L, Watson L, Merrell M, Dahmen H, Heinrich PC, Muller-Newen G, Harris KW. Inhibition of gp130 signaling in breast cancer blocks constitutive activation of Stat3 and inhibits in vivo malignancy. Cancer Res. 2004;64:6924–33.

    Article  CAS  PubMed  Google Scholar 

  132. Bachelot T, Ray-Coquard I, Menetrier-Caux C, Rastkha M, Duc A, Blay JY. Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer. 2003;88:1721–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M, Ceccarelli C, Santini D, Paterini P, Marcu KB, et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest. 2007;117:3988–4002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Visvader JE. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Dev. 2009;23:2563–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.

    Article  PubMed  Google Scholar 

  136. Glas AM, Floore A, Delahaye LJ, Witteveen AT, Pover RC, Bakx N, Lahti-Domenici JS, Bruinsma TJ, Warmoes MO, Bernards R, et al. Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics. 2006;7:278.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Fridman JS, Hernando E, Hemann MT, de Stanchina E, Cordon-Cardo C, Lowe SW. Tumor promotion by Mdm2 splice variants unable to bind p53. Cancer Res. 2003;63:5703–6.

    CAS  PubMed  Google Scholar 

  138. Bartel F, Taubert H, Harris LC. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell. 2002;2:9–15.

    Article  CAS  PubMed  Google Scholar 

  139. Okumura N, Yoshida H, Kitagishi Y, Nishimura Y, Matsuda S. Alternative splicings on p53, BRCA1 and PTEN genes involved in breast cancer. Biochem Biophys Res Commun. 2011;413:395–9.

    Article  CAS  PubMed  Google Scholar 

  140. Simoncic PD, Bourdeau A, Lee-Loy A, Rohrschneider LR, Tremblay ML, Stanley ER, McGlade CJ. T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation. Mol Cell Biol. 2006;26:4149–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

T.T. is a National Health and Medical Research Council (NHMRC) of Australia Principal Research Fellow and supported by grants from the NHMRC.

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  1. Department of Biochemistry and Molecular Biology, Monash University, Victoria, 3800, Australia

    Tony Tiganis

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  1. Laura and Isaac Perlmutter Cancer Center, NY, New York, USA

    Benjamin G. Neel

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA

    Nicholas K. Tonks

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Tiganis, T. (2016). The Role of TCPTP in Cancer. In: Neel, B., Tonks, N. (eds) Protein Tyrosine Phosphatases in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3649-6_5

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