CIP2A is an intracellular endogenous protein phosphatase 2A (PP2A) inhibitor with oncogenic activities. CIP2A was initially identified as a tumor-associated antigen (TAA) in gastric and liver cancer patients, and it was overexpressed in a variety of cancer types. Recently, we found that CIP2A was overexpressed in human lung cancer specimens as compared to normal lung tissues. The elevated expression of CIP2A in lung cancer cells results in an increased cell proliferation. The observation on the association between CIP2A and AKT phosphorylation at S473 in our lab and other labs suggested the role of CIP2A in regulating AKT phosphorylation. Our preliminary data indicated that CIP2A might promote cell proliferation through AKT signaling pathway under growth factor stimulation. Interestingly, the depletion of CIP2A in lung cancer cells did not induce a global change of AKT phosphatase activity, which implied that CIP2A might recognize specific AKT targets and play certain roles in the signaling pathway. In this study, we identified several AKT substrates specifically targeted by CIP2A, such as Hsp70 and mTOR, by proteomic-based systematic screening. The candidates obtained from our study will expand the understanding on protein-substrate interaction and therefore direct the cancer drug design. Therefore, our study addressed a novel role of CIP2A in mediating cancer progression through interacting with AKT pathway in a substrate-dependent manner.

Citation Format: Ningjing Lei, Bo Peng, Jiangying Zhang. CIP2A regulates cell proliferation via akt signaling pathway in human lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3350. doi:10.1158/1538-7445.AM2014-3350