SH2-Domain containing inositol 5-phosphatases (SHIP1 & SHIP2) dephosphorylate the 5-position of PI(3,4,5)P3 generating PI(3,4)P2. PI(3,4)P2 activates Protein Kinase B (PKB/Akt) and promotes cell survival. SHIP2 expression and activity is increased in colorectal cancer suggesting an oncogenic role. Treatment of colorectal cancer cells with K149 (2uM) decreases PKB/Akt signaling and sensitizes the cells to 5-fluorouracil regardless of whether the cell lines have a PI3KCA mutation.
1) E. Hoekstra, A.H. Das, et al. “Lipid phosphatase SHIP2 functions as oncogene in colorectal cancer by regulating PKB activation” Oncotarget 2016; 7:73525-73540. DOI: 10.18632/oncotarget.12321