EFEMP1 promotes ovarian cancer cell growth, invasion and metastasis via activated the AKT pathway

// Xiuxiu Yin 1, 2 , Shuang Fang 3 , Mei Wang 4 , Qiang Wang 5 , Rui Fang 6 , Jie Chen 1 1 Department of Maternal and Child Health, School of Public Health, Shandong University, Jinan, 250012, China 2 The No.1 People’s Hospital of Jining, Jining 272000, China 3 Biochemistry and Molecular Biology, Georgetown University, Georgetown, Washington D.C, 20057, USA 4 Pharmacy Department, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250012, China 5 Department of Obstetrics and Gynecology, the Second Hospital affiliated to Jilin University, Jilin, 130000, China 6 Clinical Medicine, School of Medicine, Shandong University, Jinan 250012, China Correspondence to: Jie Chen, email: 77chenjie@sdu.edu.cn Keywords: EFEMP1, ovarian cancer, invasion, metastasis, EMT Received: March 14, 2016      Accepted: June 09, 2016      Published: June 25, 2016 ABSTRACT EFEMP1, a kind of extracellular matrix (ECM) protein, has been suggested to correlate with the development of different types of carcinoma. However, its functions in ovarian cancer remain unclear. In our study, we performed cDNA microarray analysis and identified EFEMP1 dramatically elevated in the highly invasive subclone, compared with the low invasive subclone. Lentivirus transfection experiments were constructed afterwards. The results demonstrated that knockdown of EFEMP1 significantly inhibited ovarian cancer cell proliferation and induced cell cycle arrest at the G1/G0 phase. We also found that decreased the activity of phospho-AKT could suppress cell invasion and metastasis. Meanwhile, the increased phospho-AKT activity induced by the overexpression of EFEMP1 had significantly enhanced the abilities of ovarian cancer cells to invade and migrate. In addition, the vivo nude mice model confirmed that EFEMP1 was tightly correlated with the development of tumor. The results of RT 2 Profiler EMT PCR array further indicated that decreased EFEMP1 suppressed epithelial-to-mesenchymal transition (EMT). Collectively, by activating AKT signaling pathway, EFEMP1 contributed to ovarian cancer invasion and metastasis as a positive regulator. Overall, EFEMP1 had showed the potential use in the development of new therapeutic strategies for ovarian cancer.