Conversely, knockdown of both PIPP and PTEN resulted in increased AKT phosphorylation compared with knockdown of either phosphatase alone suggesting that combined loss of PIPP and PTEN may additively hyperactivate PI3K/AKT signalling in melanoma cells [107], consistent with the contention that PIPP and PTEN play non-redundant roles in regulating PtdIns(3,4,5)P3-dependent signalling. This evidence concerns the gene AKT1 and melanoma.