Phosphatases usually form an integrated structure with differentsubstrate speci!city by combining the same core structural subunitswith different regulatory subunits. Previous studies have reported thata peptide named STRN3 can bind to PP2Aa, the scaffolding subunit ofPP2A, and enhance the dephosphorylation of PP2A on MST, thusslowing the progression of gastric cancer (36). In our study, PDHPS1 did not change the phosphorylation level of MST, which may accountfor PDHPS1 regulating a different subunit of PP2A and affecting theaf!nity or activity of PP2A to different substrates. The property ofenzyme speci!city to substrate could avoid the effect of PP2A on othersubstrates or pathways, thus avoiding drug side effects. In addition,because both MST and YAP are important regulatory factors in theHippo pathway, and MST is the direct upstream of YAP, it is suggestedthat the combination of PDHPS1 and STRN3 may produce synergisticinhibition of the Hippo pathway and play a more powerful role intumor inhibition.