Wang F.Zhou S.Qi D.Xiang S.-H.Wong E.T.Wang X.Fonkem E.Hsieh T.-C.Yang J.Kirmani B.Shabb J.B.Wu J.M.Wu M.Huang J.H.WEI-HSUAN YUWu E.2020-02-062020-02-0620190002-7863https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061899738&doi=10.1021%2fjacs.8b12872&partnerID=40&md5=e6b42fa7e1b47c8784251e4c9a988431https://scholars.lib.ntu.edu.tw/handle/123456789/454691The aim of this study is to illuminate a novel therapeutic approach by identifying a functional binding target of salinomycin, an emerging anticancer stem cell (CSC) agent, and to help dissect the underlying action mechanisms. By utilizing integrated strategies, we identify that nucleolin (NCL) is likely a salinomycin-binding target and a critical regulator involved in human neuroblastoma (NB) CSC activity. Salinomycin markedly suppresses NB CD34 expression and reduces CD34+ cell population in an NCL-dependent manner via disruption of the interaction of NCL with CD34 promoter. The elevated levels of NCL expression in NB tumors are associated with poor patient survival. Altogether, these results indicate that NCL is likely a novel functional salinomycin-binding target that exhibits the potential to be a prognostic marker for NB therapy. ? 2019 American Chemical Society.[SDGs]SDG3Cell culture; Cell proliferation; Action mechanisms; Binding proteins; Elevated level; Human neuroblastoma; Integrated strategy; Neuroblastomas; Patient survivals; Prognostic markers; Stem cells; binding protein; CD34 antigen; nucleolin; salinomycin; antineoplastic agent; CD34 antigen; nucleolin; phosphoprotein; pyran derivative; RNA binding protein; salinomycin; antigen expression; antineoplastic activity; antiproliferative activity; Article; cancer prognosis; cancer recurrence; cancer stem cell; cancer survival; cell population; controlled study; drug protein binding; drug targeting; human; human cell; inhibition kinetics; neuroblastoma; promoter region; protein expression; protein interaction; binding site; biosynthesis; cancer stem cell; cell proliferation; chemistry; drug effect; drug screening; metabolism; neuroblastoma; pathology; tumor cell culture; Antigens, CD34; Antineoplastic Agents; Binding Sites; Cell Proliferation; Drug Screening Assays, Antitumor; Humans; Neoplastic Stem Cells; Neuroblastoma; Phosphoproteins; Pyrans; RNA-Binding Proteins; Tumor Cells, Culturedjournal article10.1021/jacs.8b128722-s2.0-85061899738