Role of Protein Tyrosine Phosphatases in Cancer Signaling

  • Elie Kostantin
  • Yevgen Zolotarov
  • Michel L. TremblayEmail author


Protein tyrosine phosphatases (PTPs) constitute a large family of enzymes that can exert both positive and negative effects on signaling pathways. With 107 members, the PTP gene family is one of the most diverse in the mammalian genome. Since most previously described oncogenes were kinases, it was logical to postulate that PTPs would, therefore, act as tumor suppressor genes. However, it is now clear that within the PTP family there are also many pro-oncogenic enzymes. Herein, we selected five key PTPs (PTEN, SHP2, PRL, TC-PTP, PTP1B) known to modulate oncogenic signaling which are therefore of great interest as predictive markers. Despite 40 years of research since their discovery, the PTP gene family remains poorly characterized. With their increasingly recognized function in cancer cell signaling, we should expect that PTPs will be further used as biomarkers and therapeutic targets.




  1. 1.
    Worby CA, Dixon JE. PTEN. Annu Rev Biochem. 2014;83(1):641–69.CrossRefPubMedGoogle Scholar
  2. 2.
    Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Ann Rev Pathol Mech Dis. 2009;4(1):127–50.CrossRefGoogle Scholar
  3. 3.
    Gabriel K, Ingram A, Austin R, Kapoor A, Tang D, Majeed F, et al. Regulation of the tumor suppressor PTEN through exosomes: a diagnostic potential for prostate cancer. PLoS One. 2013;8(7):e70047.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Rubio T, Kohn M. Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3. Biochem Soc Trans. 2016;44(5):1305–12.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1–46.CrossRefPubMedGoogle Scholar
  6. 6.
    Hardy S, Uetani N, Wong N, Kostantin E, Labbe DP, Begin LR, et al. The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis. Oncogene. 2015;34(8):986–95.CrossRefPubMedGoogle Scholar
  7. 7.
    Thura M, Al-Aidaroos AQ, Yong WP, Kono K, Gupta A, Lin YB, et al. PRL3-zumab, a first-in-class humanized antibody for cancer therapy. JCI Insight. 2016;1(9):e87607.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chan G, Neel BG. Role of PTPN11 (SHP2) in cancer. In: Protein tyrosine phosphatases in cancer. New York: Springer; 2016. p. 115–43.CrossRefGoogle Scholar
  9. 9.
    Grossmann KS, Rosario M, Birchmeier C, Birchmeier W. The tyrosine phosphatase Shp2 in development and cancer. Adv Cancer Res. 2010;106:53–89.CrossRefPubMedGoogle Scholar
  10. 10.
    Julien SG, Dube N, Hardy S, Tremblay ML. Inside the human cancer tyrosine phosphatome. Nat Rev Cancer. 2011;11(1):35–49.CrossRefGoogle Scholar
  11. 11.
    Tiganis T. The Role of TCPTP in cancer. In: Protein tyrosine phosphatases in cancer. New York: Springer; 2016. p. 145–68.CrossRefGoogle Scholar
  12. 12.
    Kleppe M, Lahortiga I, El Chaar T, De Keersmaecker K, Mentens N, Graux C, et al. Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nat Genet. 2010;42(6):530–5.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Labbé DP, Tremblay ML. PTP1B: from metabolism to cancer. 263. New York: Springer; 2016. p. 169–99.Google Scholar
  14. 14.
    Feldhammer M, Uetani N, Miranda-Saavedra D, Tremblay ML. PTP1B: a simple enzyme for a complex world. Crit Rev Biochem Mol Biol. 2013;48(5):430–45.CrossRefPubMedGoogle Scholar
  15. 15.
    Arias-Romero LE, Saha S, Villamar-Cruz O, Yip S-C, Ethier SP, Zhang Z-Y, et al. Activation of Src by protein tyrosine phosphatase 1B is required for ErbB2 transformation of human breast epithelial cells. Cancer Res. 2009;69(11):4582–8.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Pike KA, Tremblay ML. TC-PTP and PTP1B: regulating JAK–STAT signaling, controlling lymphoid malignancies. Cytokine. 2016;82:52–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Gunawardana J, Chan FC, Telenius A, Woolcock B, Kridel R, Tan KL, et al. Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Nat Genet. 2014;46(4):329–35.CrossRefPubMedGoogle Scholar
  18. 18.
    Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 2014;24(6):766–9.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Truong M, Yang B, Jarrard DF. Toward the detection of prostate cancer in urine: a critical analysis. J Urol. 2013;189(2):422–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Penafuerte C, Feldhammer M, Mills JR, Vinette V, Pike KA, Hall A, et al. Downregulation of PTP1B and TC-PTP phosphatases potentiate dendritic cell-based immunotherapy through IL-12/IFNgamma signaling. Oncoimmunology. 2017;6(6):e1321185.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Elie Kostantin
    • 1
  • Yevgen Zolotarov
    • 1
  • Michel L. Tremblay
    • 1
    Email author
  1. 1.Department of BiochemistryGoodman Cancer Research Center, McGill UniversityMontrealCanada

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