PTP1B: From metabolism to 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.