| Cancerous inhibitor of PP2A (CIP2A) is an intracellular endogenous protein phosphatase 2A (PP2A) inhibitor with oncogenic activities. Initially identified as a tumor-associated antigen (TAA) in gastric and liver cancer patients, CIP2A was overexpressed in a variety of cancer types. And the overexpression of CIP2A in cancer cell is associated with increased cell proliferation and decreased cell apoptosis. However, the mechanism of CIP2A in cancer progression is still poorly understood. Here, we reported the evidence that CIP2A can regulate AKT phosphorylation at S473 under growth factor stimulation and our results also showed that CIP2A might regulate cell proliferation and cell apoptosis through the AKT signaling pathway. Interestingly, depletion of CIP2A did not induce a global change of AKT phosphatase activity, which implied that CIP2A might recognize specific AKT targets and play certain roles in this signaling pathway. In addition, we also detected that CIP2A expression was associated with AKT downstream substrates, such as GRP78 and mTOR phosphorylation. Therefore, our studies addressed a novel role of CIP2A in mediating cancer progression through interacting with specific AKT substrates. |
