As another example, PTEN is a well-known tumor suppressor that negatively regulates cell proliferation, migration, and angiogenesis by antagonizing the PI3K-Akt/mTOR pathway [38, 39]; however, PTEN could also enhance PNCK-mediated-ERK1/2 inhibition to promote cellular proliferation, as well as cause FOXO-dependent upregulation of p53 suppressor Bcl6 and allow tumor cells to escape p53- and p21-mediated cellular senescence in leukemia [40]. This evidence concerns the gene MAPK3 and neoplasm.