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Biochemistry - Gastroenterology and Hepatology - Oncology - Surgery


Hypoxia-Inducible Factor-1a Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene
Published: Monday, August 27, 2012
Author: Tiansuo Zhao et al.

by Tiansuo Zhao, Song Gao, Xiuchao Wang, Jingcheng Liu, Yitao Duan, Zhanna Yuan, Jun Sheng, Shasha Li, Feng Wang, Ming Yu, He Ren, Jihui Hao

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; 5'-A/GCGTG-3') 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 demonstrated that HIF-1a may regulate cancer cell migration through CX3CR1. The HIF-1a/CX3CR1 pathway might represent a valuable therapeutic target to prevent invasion and distant metastasis in PDAC.
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