Inside the human cancer tyrosine phosphatome

Key Points The protein tyrosine phosphatase (Ptp) family comprises 107 members that are classified into four classes on the basis of the amino acid sequences of their catalytic domains. Recent evidence has shown that members of the Ptp family are key components of tumorigenesis in various human cancers, exerting either putative oncogenic or tumour suppressive functions, depending on the cellular context. Genetic alterations such as mutation, deletion and amplification are the most important features for putative oncogenic PTPs, whereas in most cases epigenetic modifications such as DNA methylation counter the tumour suppressive functions of PTPs. Recent advances have begun to decipher the molecular mechanisms by which putative oncogenic PTPs may drive tumorigenesis in human cells. Proliferation, survival, apoptosis, vesicular trafficking, adhesion, migration and invasion are all altered by the aberrant functions of PTPs during tumour development. Evidence for an association between PTPs and an increased risk of developing cancer remains controversial and elusive. Here, we focus on the pertinent genetic and functional data that support the relevance of members of the Ptp family to human cancer. PTP inhibitors are currently being developed. However, a better understanding of the basic biology of PTPs in human tumour development will be required to improve the therapeutic use of such inhibitors. The protein tyrosine phosphatase (Ptp) family dephosphorylates target proteins and counters the activities of protein tyrosine kinases. Accumulating evidence indicates that some PTPs have an important role in the inhibition or control of growth, whereas some PTPs exert oncogenic functions. This Review discusses the relevance of PTPs to cancer biology and their potential as therapeutic targets. Members of the protein tyrosine phosphatase (Ptp) family dephosphorylate target proteins and counter the activities of protein tyrosine kinases that are involved in cellular phosphorylation and signalling. As such, certain PTPs might be tumour suppressors. Indeed, PTPs play an important part in the inhibition or control of growth, but accumulating evidence indicates that some PTPs may exert oncogenic functions. Recent large-scale genetic analyses of various human tumours have highlighted the relevance of PTPs either as putative tumour suppressors or as candidate oncoproteins. Progress in understanding the regulation and function of PTPs has provided insights into which PTPs migh