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PTP1B: From Metabolism to Cancer

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Protein Tyrosine Phosphatases in Cancer

Abstract

More than 25 years after its discovery, the prototypic protein-tyrosine phosphatase, PTP1B, remains at the forefront of research in the phosphatase field. In this chapter, we summarize its role in metabolic diseases that have heavily contributed to the development of targeted inhibitors. It is now clear that metabolism can be an active contributor to tumorigenesis and intriguingly some PTP1B substrates are known to play a central role in these diseases. In cancer, PTP1B acts on an array of cancer-related substrates including a variety of receptor tyrosine kinases. Because the range of PTP1B substrates generate a complex signaling network, ascertaining the net effect of PTP1B activity on tumorigenesis in a particular context proves to be a challenging task. Along this line, we discuss some of the most characterized systems in which PTP1B has been proven to act as an oncogene. Because PTP1B is ubiquitously expressed and acts on numerous substrates across all cell types, it is clear that its gene and protein regulation is critical for its specificity and in maintaining cellular homeostasis. Therefore, we have highlighted some of the important mechanisms of PTP1B regulation in relation to cancer, including its role on endocytosis, that are likely to influence a broader range of oncogenic processes. In conclusion, we present our thoughts on important questions relative to PTP1B as a target in cancer treatment.

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Acknowledgements

We thank Noriko Uetani for technical assistance with figure design and drawing and Teri Hatzihristidis for a critical review of the manuscript. D.P.L. is a recipient of Canadian Institute of Health Research (CIHR) Frederick Banting and Charles Best doctoral research award and the CIHR/Fonds de la Recherche en Santé du Québec (FRSQ) training grant in cancer research FRN53888 of the McGill Integrated Cancer Research Training Program. M.L.T. is a Jeanne and Jean-Louis Lévesque chair in Cancer Research.

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  1. Division of Experimental Medicine, Department of Medicine, Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue, Room 601, Montréal, QC, Canada, H3A 1A3

    David P. Labbé & Michel L. Tremblay

  2. Department of Biochemistry and Oncology, McGill University, Montréal, QC, Canada

    Michel L. Tremblay

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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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Labbé, D.P., Tremblay, M.L. (2016). PTP1B: From Metabolism to 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_6

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