title: Hypoxia increases CX3CR1 expression via HIF-1 and NF‑κB in androgen-independent             prostate cancer cells.
abstract: The unique CX3C chemokine CX3CL1 and its cognate receptor CX3CR1 have been             implicated in organ-specific metastasis of various types of tumors. Hypoxia, a             common phenomenon in solid tumors, is associated with a malignant cancer phenotype.             Previous studies have proved that hypoxia facilitates cancer cell metastasis through             upregulation of specific chemokine receptors. We hypothesized that hypoxia could             upregulate CX3CR1 expression and lead to an increased chemotactic response to             CX3CL1 in prostate cancer cells. In the present study, we found that CX3CR1 expression             was significantly increased in androgen-independent prostate cancer cells, including             DU145, PC-3 and PC-3M, following exposure to hypoxia. This upregulation of CX3CR1             corresponded to a significant increase in migration and invasion of prostate cancer             cells under hypoxic conditions, which was attenuated after knocking down CX3CR1             expression. In addition, we examined the possible role of HIF-1 and NF-κB in the             process of hypoxia-induced CX3CR1 expression and hypoxia-mediated metastasis.             Attenuation of HIF-1 and NF-κB transcriptional activity by siRNAs or pharmacological             inhibitors, abrogated hypoxia-induced upregulation of CX3CR1, and also prevented             the migration and invasion of DU145 cells under a hypoxic environment. In summary,             our study demonstrated that HIF-1 and NF-κB are essential for hypoxia-regulated             CX3CR1 expression, which is associated with increased migratory and invasive potential             of prostate cancer cells. CX3CR1 signaling is a potential therapeutic target in             the adjuvant treatment of prostate cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin 150081, Heilongjiang, PR China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Xiao
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Lin
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zou
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Li-Nan
authors.initials: LN
authors.lastname: Zhao
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Jie-Bing
authors.initials: JB
authors.lastname: Tang
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Zheng
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Yu
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019707:Receptors, Chemokine / Q000235:genetics*
chemical_list: D000728:Androgens; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D051793:Hypoxia-Inducible Factor 1; D016328:NF-kappa B; D019707:Receptors, Chemokine