title: The oncoprotein HBXIP up-regulates FGF4 through activating transcriptional factor Sp1 to promote the migration of breast cancer cells.
abstract: We have reported that the oncoprotein hepatitis B X-interacting protein (HBXIP) is able to promote migration of breast cancer cells. Fibroblast growth factor 4 (FGF4) is a multipotent growth factor and is highly expressed in various human cancers. However, the regulatory mechanism of FGF4 in breast cancer remains poorly understood. In the present study, we report that HBXIP is able to up-regulate FGF4 to enhance the migration of breast cancer cells. Immunohistochemistry staining showed that HBXIP and FGF4 were highly expressed in clinical metastatic lymph nodes of breast tumor. The expression levels of HBXIP were positively related to those of FGF4 in clinical breast cancer tissues. Then, we validated that HBXIP up-regulated the expression of FGF4 at the levels of promoter, mRNA and protein by luciferase reporter gene assays, reverse transcription-polymerase chain reaction and Western blot analysis. Moreover, we found that HBXIP was able to activate FGF4 promoter through transcriptional factor Sp1 by luciferase reporter gene assays. Chromatin immunoprecipitation assays confirmed that HBXIP coactivated Sp1 to stimulate FGF4 promoter. In function, we showed that HBXIP promoted breast cancer cell migration through FGF4 by wound healing and transwell cell migration assays. Thus, we conclude that the oncoprotein HBXIP up-regulates FGF4 through activating transcriptional factor Sp1 to promote the migration of breast cancer cells. Therapeutically, HBXIP may serve as a novel target in breast cancer.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Runping
authors.initials: R
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Peijian
authors.initials: P
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: yelihong@nankai.edu.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D051519:Fibroblast Growth Factor 4 / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; C110719:LAMTOR5 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human
keywords: Breast cancer; FGF4; HBXIP; Migration; Sp1