CIP2A Cooperates with H-Ras to Promote Epithelial-mesenchymal Transition in Cervical-cancer Progression

The oncoprotein Cancerous Inhibitor of PP2A (CIP2A) has been reported to interact with Protein phosphatase 2 (PP2A) to stabilize c-Myc and prevent its degradation, and high expression levels of CIP2A have been proved to be related to poor clinical outcomes in multiple cancers. Here, we not only proved that the expression of CIP2A is positively correlated with lymph-node metastasis and cervical-cancer progression, but also revealed a close correlation between the protein's expression and the expression levels of two core epithelial-to-mesenchymal transition (EMT) markers, Vimentin and Snail. In addition, we manipulated CIP2A expression to regulate EMT conversion and employed a pull-down assay, mass-spectrometric (MS) peptide sequencing, as well as bilateral co-immunoprecipitation to identify potentially interacting proteins in cervical-cancer cells. In this study, we proposed and successfully proved, for the first time, that CIP2A physically associates with H-Ras, which leads to the activation of the MEK/ERK signaling pathway and promotes EMT and cervical-cancer progression. Based on our observations and prior findings that CIP2A participates in c-Myc regulation, we conjecture that CIP2A may be a potentially promising molecular target for the adoptive therapy of human cancer.