is likely the cause of the increased cell migration observed following PTPkappa cleavage. Shedding of PTPkappa may also be regulated by the presence of galectin-3 binding protein, as has been shown in WiDr cells. The authors suggest that the ratio of galectin-3 binding protein to galectin 3 influences the cleavage and shedding of PTPkappa, although the exact mechanism of how these proteins regulate PTPkappa cleavage was not determined. By reactive oxygen species in cancer One mechanism whereby PTPkappa tyrosine phosphatase activity can be perturbed in cancer is via oxidative inhibition mediated by reactive oxygen species generated by either hydrogen peroxide in vitro or UV irradiation of skin cells in vivo. In cell-free assays, the presence of hydrogen peroxide reduces PTPkappa tyrosine phosphatase activity and increases EGFR tyrosine phosphorylation. UV-irradiation of primary human keratinocytes yields the same results, namely a reduction of PTPkappa tyrosine phosphatase activity and an increase in EGFR tyrosine phosphorylation. EGFR phosphorylation then leads to cell proliferation, suggesting that PTPkappa may function as a tumor suppressor in skin cancer in addition to melanoma. Expression PTPkappa is expressed in human keratinocytes. TGFβ1 is a growth inhibitor in human keratinocytes. Stimulation of the cultured human keratinocyte cell line, HaCaT, with TGFβ1 increases the levels of PTPkappa (PTPRK) mRNA as assayed by northern blot analysis. TGFβ1 also increased PTPkappa mRNA and protein in normal and tumor mammary cell lines. HER2 overexpression reduced PTPkappa mRNA and protein expression. Clinical significance Melanoma and skin cancer Expression analysis of PTPkappa mRNA in normal melanocytes and in melanoma cells and tissues demonstrated that PTPkappa is downregulated or absent 20% of the time in melanoma, suggesting that PTPkappa is a tumor suppressor gene in melanoma. A form of PTPkappa with a point mutation in the fourth fibronectin III repeat was identified to be a melanoma specific antigen recognized by CD4+ T cells in a melanoma patient with 10-year tumor-free survival after lymph node resection. This particular mutated form of PTPkappa was not identified in 10 other melanoma cell lines, and may thus represent a unique mutation in one patient. Lymphoma PTPkappa was also identified as the putative tumor suppressor gene commonly deleted in primary central nervous system lymphomas (PCNSLs). Downregulation of PTPkappa was found to occur following Epstein-Barr Virus (EBV) infection of Hodgkin’s Lymphomas cells. Colorectal cancer Using a transposon-based genetic screen, researchers found that disruption of the PTPRK gene in gastrointestinal tract epithelium resulted in