DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis

// Xiaoqing Yang 1 , Xinhua Zhang 2 , Rongrong Wu 1 , Qicheng Huang 1 , Yao Jiang 1 , Jianbing Qin 2 , Feng Yao 1 , Guohua Jin 2 , Yuquan Zhang 1 1 Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, NanTong, Jiangsu 226006, People's Republic of China 2 Department of Anatomy, Nantong University, Nantong, JiangSu 226000, People’s Republic of China Correspondence to: Yuquan Zhang, email: jsnt_zhangyuquan@163.com Guohua Jin, email: jguohua@ntu.edu.cn Keywords: endometrial carcinoma, dipeptidyl peptidase IV, sitagliptin, hypoxia-inducible factor 1a, vascular endothelial growth factor A Received: May 16, 2016 Accepted: December 05, 2016 Published: January 02, 2017 ABSTRACT Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo . These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic.