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PTP1B and TC-PTP: regulators of transformation and tumorigenesis

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Abstract

PTP1B and T cell PTP (TC-PTP) are protein tyrosine phosphatases (PTPs) that share high sequence and structural homology yet play distinct physiological roles. While PTP1B plays a central role in metabolism and is an attractive drug target for obesity and type 2 diabetes, TC-PTP is necessary for the control of inflammation. In this review, we will discuss the growing evidence for the involvement of PTP1B in cancer, while proposing a role for TC-PTP in inflammation-induced tumorigenesis. Given the challenge of developing inhibitors specific for PTP1B alone, it is necessary to consider both enzymes and their roles in various cancer models.

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Abbreviations

CSF1R:

macrophage colony stimulating factor 1 receptor

DLBCL:

diffuse large B cell lymphoma

ECM:

extracellular matrix

EGFR:

epidermal growth factor receptor

ER:

endoplasmic reticulum

IFN-γ:

interferon γ

IGF1-R:

insulin-like growth factor 1 receptor

IL:

interleukin

iNOS:

inducible nitric oxide synthase

IR:

insulin receptor

JAK:

Janus kinase

LPS:

lipopolysaccharide

NLS:

nuclear localization signal

NO:

nitric oxide

PDGFR:

platelet-derived growth factor receptor

PI3K:

phosphatidylinositol 3-kinase

PTK:

protein tyrosine kinase

PTP:

protein tyrosine phosphatase

RTK:

receptor PTK

STAT:

signal transducer and activator of transcription

TAg:

large T antigen

TNF-α:

tumor necrosis factor α

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Acknowledgements

The authors would like to thank Maxime Hallé and Adam Scott for critical reading of the manuscript, members of the Tremblay laboratory for helpful discussions, and Dr. Noriko Uetani for preparing Fig. 1. KMD and MS are recipients of Fonds de la recherche en santé du Québec doctoral awards. MLT is a Jeanne and Jean-Louis Lévesque chair in Cancer Research. This work has been supported by operating grants to MLT from the Canadian Institutes of Health Research (MOP-62887) and the National Cancer Institute of Canada (015200).

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  1. McGill Cancer Centre and Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, Canada, H3G 1Y6

    Matthew Stuible, Karen M. Doody & Michel L. Tremblay

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Correspondence to Michel L. Tremblay.

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Matthew Stuible and Karen M. Doody contributed equally to this work.

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Stuible, M., Doody, K.M. & Tremblay, M.L. PTP1B and TC-PTP: regulators of transformation and tumorigenesis. Cancer Metastasis Rev 27, 215–230 (2008). https://doi.org/10.1007/s10555-008-9115-1

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