Overexpression of PP2A inhibitor SET oncoprotein is associated with tumor progression and poor prognosis in human non-small cell lung cancer

// Hao Liu 1 , Yixue Gu 1 , Hongsheng Wang 2 , Jiang Yin 1 , Guopei Zheng 1 , Zhijie Zhang 1 , Minyin Lu 1 , Chenkun Wang 1 and Zhimin He 1 1 Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, PR China 2 Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China Correspondence to: Zhimin He, email: // Keywords : SET oncoprotein, non-small cell lung cancer, PP2A, FTY720 Received : January 28, 2015 Accepted : March 29, 2015 Published : April 14 ,2015 Abstract SET oncoprotein is an endogenous inhibitor of protein phosphatase 2A (PP2A), and SET-mediated PP2A inhibition is an important regulatory mechanism for promoting cancer initiation and progression of several types of human leukemia disease. However, its potential relevance in solid tumors as non-small cell lung cancer (NSCLC) remains mostly unknown. In this study, we showed that SET was evidently overexpressed in human NSCLC cell lines and NSCLC tissues. Clinicopathologic analysis showed that SET expression was significantly correlated with clinical stage ( p < 0.001), and lymph node metastasis ( p < 0.05). Kaplan-Meier analysis revealed that patients with high SET expression had poorer overall survival rates than those with low SET expression. Moreover, knockdown of SET in NSCLC cells resulted in attenuated proliferative and invasive abilities. The biological effect of SET on proliferation and invasion was mediated by the inhibition of the PP2A, which in turn, activation of AKT and ERK, increased the expression of cyclin D1 and MMP9, and decreased the expression of p27. Furthermore, we observed that restoration of PP2A using SET antagonist FTY720 impaired proliferative and invasive potential in vitro , as well as inhibited tumor growth in vivo of NSCLC cells. Taken together, SET oncoprotein plays an important role in NSCLC progression, which could serve as a potential prognosis marker and a novel therapeutic target for NSCLC patients.