title: RanBPM inhibits BLT2-mediated IL-8 production and invasiveness in aggressive breast cancer cells.
abstract: RanBPM is a scaffolding protein that regulates several cellular processes by interacting with various proteins. Previously, we reported that RanBPM acts as a negative regulator of BLT2, a low-affinity leukotriene B4receptor; thus, it interferes with BLT2-mediated cell motility. In the present study, we observed that the expression levels of RanBPM were markedly reduced in the highly aggressive MDA-MB-435 and MDA-MB-231 human breast cancer cell lines compared with those in non-invasive MCF-7 cells. Additionally, we found that the restoration of RanBPM levels suppressed the invasiveness of these aggressive breast cancer cells in a manner dependent on BLT2 activation. In contrast, the knockdown of endogenous RanBPM by shRNA strongly promoted invasiveness in non-invasive MCF-7 cells. We also observed that RanBPM suppressed the invasiveness of aggressive breast cancer cells by inhibiting BLT2-mediated reactive oxygen species (ROS) generation and IL-8 production. Taken together, our results suggest that RanBPM acts as a negative regulator of BLT2, thus attenuating the invasiveness of aggressive breast cancer cells.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul, 02841, South Korea.
authors.forename: Jun-Dong
authors.initials: JD
authors.lastname: Wei
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul, 02841, South Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Jang
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul, 02841, South Korea. Electronic address: jhongkim@korea.ac.kr.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C508606:CXCL8 protein, human; D003598:Cytoskeletal Proteins; D016209:Interleukin-8; C485878:LTB4R2 protein, human; D009687:Nuclear Proteins; C116005:Ran binding protein 9; D017382:Reactive Oxygen Species; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4
keywords: BLT2; Breast cancer; IL-8; Invasiveness; RanBPM