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 B4 receptor; 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 MDAMB- 435 and MDA-MB-231 human breast cancer cell lines compared with those in non-invasive MCF7 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 BLT2mediated 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. (C) 2016 Elsevier Inc. All rights reserved.