Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells

Abstract

BackgroundsTamoxifen is typically used to treat patients with estrogen receptor alpha (ERα)-positive breast cancer. However, 30% of these patients gain acquired resistance to tamoxifen during or after tamoxifen treatment. As a Ras modulator, Nogo-B receptor (NgBR) is required for tumorigenesis through the signaling crosstalk with epidermal growth factor (EGF) receptor (EGFR)-mediated pathways. NgBR is highly expressed in many types of cancer cells and regulates the sensitivity of hepatocellular carcinoma to chemotherapy. In this study, we found the expression of NgBR is increased in tamoxifen-resistant ERα-positive breast cancer cells.MethodsTamoxifen-resistant ERα-positive MCF-7 and T47D breast cancer cell lines were established by culturing with gradually increased concentration of 4-hydroxytamoxifen (4-OHT). The effects of NgBR on tamoxifen resistance was determined by depleting NgBR in these cell lines using previously validated small interfering RNA (siRNA). The effects of 4-OHT on cell viability and apoptosis were determined using well-accepted methods such as clonogenic survival assay and Annexin V/propidium iodide staining. The alteration of EGF-stimulated signaling and gene expression was determined by western blot analysis and real-time PCR, respectively.ResultsNgBR knockdown with siRNA attenuates EGF-induced phosphorylation of ERα and restores the sensitivity to tamoxifen in ERα-positive breast cancer cells. Mechanistically, our data demonstrated that NgBR knockdown increases the protein levels of p53 and decreases survivin, which is an apoptosis inhibitor.ConclusionsThese results suggested that NgBR is a potential therapeutic target for increasing the sensitivity of ERα-positive breast cancer to tamoxifen.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1028-5) contains supplementary material, which is available to authorized users.

NOGOB receptor–mediated RAS signaling pathway is a target for suppressing proliferating hemangioma

“…Our previous results indicated that the hydrophobic cytosolic domain of NGBR binds farnesylated RAS ( 26 ). We previously demonstrated that NGBR is essential for RAS plasma membrane translocation in tumor cells, and NGBR overexpression recapitulates the oncogenic functions of RAS in cell transformation and tumor growth ( 26 , 33 , 61 – 63 ). Here, we further elucidate the roles of NGBR in regulating malignancy of proliferating hemangioma.…”

Artesunate Regulates Neurite Outgrowth Inhibitor Protein B Receptor to Overcome Resistance to Sorafenib in Hepatocellular Carcinoma Cells

“…In a previous study, Gao et al discovered that increased NgBR can enhance EGF-stimulated Ras activation and phosphorylation of AKT and ERK in tamoxifen-resistant breast cancer cells ( Gao et al, 2018 ). Moreover, NgBR expression is associated with non-small cell lung cancer (NSCLC) development and increases Snail 1 expression in NSCLC cells by MEK/ERK pathway activation ( Wu.et al, 2018 ).…”

Chitosan-Based Nanomaterials for Drug Delivery

“…Small interfering RNA (siRNA) is a double-stranded RNA of 20 to 25 nucleotides in length and has many important functions in biology [ 155 ]. It primarily plays a unique role in the RNA interference events which regulates gene expression in a specific manner.…”