title: Hypoxia-inducible factor-1α regulates chemotactic migration of pancreatic ductal adenocarcinoma cells through directly transactivating the CX3CR1 gene.
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)-1α expression was knocked down in vitro and in vivo, the expression of CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay demonstrated that HIF-1α 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-1α significantly upregulated the expression of luciferase reporter gene under the control of the CX3CR1 promoter in pancreatic cancer cells. Importantly, we demonstrated that HIF-1α may regulate cancer cell migration through CX3CR1. The HIF-1α/CX3CR1 pathway might represent a valuable therapeutic target to prevent invasion and distant metastasis in PDAC.
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Tiansuo
authors.initials: T
authors.lastname: Zhao
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Xiuchao
authors.initials: X
authors.lastname: Wang
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Liu
authors.forename: Yitao
authors.initials: Y
authors.lastname: Duan
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Yuan
authors.forename: Jun
authors.initials: J
authors.lastname: Sheng
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.forename: Jihui
authors.initials: J
authors.lastname: Hao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D002633:Chemotaxis; D002843:Chromatin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal / Q000379:methods; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D002843:Chromatin; C471885:Cx3cr1 protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008024:Ligands; D034741:RNA, Small Interfering; D019707:Receptors, Chemokine