THEM4 and neoplasm: PTEN is a widely mutated tumor suppressor gene that inhibits the oncogenic PI3K/AKT pathway.113–115 PTEN antagonizes the PI3K/Akt pathway by dephosphorylating PIP3 to PIP2,116,117 then induces changes in a variety of cellular biological functions.118,119 Carboxyl-terminal modulator protein (CTMP) could block the transmission of downstream signaling pathways by inhibiting AKT phosphorylation.120,121 PP2A has been found to dephosphorylate AKT-Thr308 and AKT-Ser473 to inhibit the activation of AKT.122,123