Protein-tyrosine phosphatases and cancer

Protein-tyrosine phosphatases (PTPs) constitute a structurally diverse family of tightly regulated enzymes that are characterized by a conserved catalytic domain with an oxidation-sensitive active-site cysteine residue.Different PTPs function as negative or positive mediators of signalling triggered by receptor-tyrosine kinases, integrins and cell-adhesion molecules.The tumour-suppressive function of PTPs is indicated by frequent inactivating mutations of PTPs in colon cancer, and the identification of Ptprj as the gene that confers colon cancer susceptibility in STS/A mice. Also, inactivation of the genes that encode SHP1 and glomerular epithelial protein 1 (GLEPP1) by methylation has been described in haematological malignancies and solid tumours, respectively.The oncogenic activity of a PTP is best characterized for the mutational activation of SHP2, which occurs in hereditary and sporadic leukaemias and, less frequently, in solid tumours.Despite technical challenges, recent advances in the design of PTP inhibitors are encouraging with respect to the possibilities of developing novel cancer drugs that function by inhibiting oncogenic PTPs.Other aspects of PTP biology that might be relevant to cancer research in the future are the regulation of PTPs by oxidation and the putative role of PTPs in angiogenesis.