hypoxia-inducible factor-1α regulates chemotactic migration of pancreatic ductal adenocarcinoma cells through directly transactivating the cx3cr1 gene低氧factor-1α调节趋化迁移胰腺导管腺癌的细胞通过直接transactivating cx3cr1基因.pdfVIP

Hypoxia-Inducible Factor-1a Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene 1. 1. 1 1 2 1 1 Tiansuo Zhao , Song Gao , Xiuchao Wang , Jingcheng Liu , Yitao Duan , Zhanna Yuan , Jun Sheng , 1 3 1 1 1 Shasha Li , Feng Wang , Ming Yu , He Ren *, Jihui Hao * 1 Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, 2 The Ministry-of-Education Key Laboratory of System Bioengineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China, 3 Institute of Chinese and Modern Medicines for Acute Abdominal Diseases, Tianjin Medical University Nankai Hospital, Tianjin, China Abstract CX3CR1 is an important chemokine receptor and regulates the chemotactic migration of pancreatic ductal adenocarcinoma (PDAC) cells. Up to now, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulates the expression of CX3CR1 in pancreatic cancer cells. When hypoxia-inducible factor (HIF)-1a expression was knocked down in vitro and in vivo, the expression of CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay demonstrated that HIF-1a bound to the hypoxia-response element (HRE; 59-A/GCGTG-39) of CX3CR1 promoter under normoxia, and this binding was significantly enhanced under hypoxia. Overexpression of HIF-1a significantly upregulated the expression of luciferase reporter gene under the control of the CX3CR1 promoter in pancreatic cancer cells. Importantly, we