Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel

Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of estrogen receptor a (ERa) positive breast cancer cases achieve a pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and promotes Ras translocation to the plasma membrane. Here, we demonstrate NgBR as a potential therapeutic target for ERa positive breast cancer patients to attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell apoptosis by modulating expression of p53 and survivin in ERa positive breast cancer cells via NgBR-mediated PI3K/Akt and MAPK/ERK signaling pathways. NgBR knockdown attenuated either 1713-estradiol or epidermal growth factor stimulated phosphorylation of ERa at Serine 118 residue. The ChIP-PCR assay further demonstrated that NgBR knockdown decreased ERa binding to the estrogen response element (ERE) of the ERa target gene and increased the binding of p53 to the promoter region of survivin to attenuate survivin transcription. In summary, our data suggest that NgBR expression is essential to promoting ERa positive breast cancer cell resistance to paclitaxel. Findings from this study implicate a novel therapeutic target for treating ERa positive breast cancer in neo-adjuvant/adjuvant chemotherapy. (C) 2018 Elsevier B.V. All rights reserved.