Mediator PTEN is also a major regulator of the PI3K/AKT signaling pathway, and it has been shown that reduced PTEN expression is accompanied by elevated PI3K/AKT pathway activity in melanoma cells, which additionally limits their inhibition by BRAF kinase, thus upregulating the MAPK pathway (also known as the RAS/RAF/MEK/ERK signaling cascade) and subsequently promoting their proliferation and survival16,17,27,30,35. The gene discussed is BRAF; the disease is melanoma.