Nucleolin is a functional binding protein for salinomycin in neuroblastoma stem cells

Fengfei Wang; Shuang Zhou; Dan Qi; Shi Hua Xiang; Eric T. Wong; Xuejing Wang; Ekokobe Fonkem; Tze Chen Hsieh; Jianhua Yang; Batool Kirmani; John B. Shabb; Joseph M. Wu; Min Wu; Jason H. Huang; Wei Hsuan Yu; Erxi Wu

doi:10.1021/jacs.8b12872

Nucleolin is a functional binding protein for salinomycin in neuroblastoma stem cells

Fengfei Wang, Shuang Zhou, Dan Qi, Shi Hua Xiang, Eric T. Wong, Xuejing Wang, Ekokobe Fonkem, Tze Chen Hsieh, Jianhua Yang, Batool Kirmani, John B. Shabb, Joseph M. Wu, Min Wu, Jason H. Huang, Wei Hsuan Yu, Erxi Wu

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31 Scopus citations

Abstract

The 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.

Original language	English (US)
Pages (from-to)	3613-3622
Number of pages	10
Journal	Journal of the American Chemical Society
Volume	141
Issue number	8
DOIs	https://doi.org/10.1021/jacs.8b12872
State	Published - Feb 27 2019

ASJC Scopus subject areas

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

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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., Yu, W. H., & Wu, E. (2019). Nucleolin is a functional binding protein for salinomycin in neuroblastoma stem cells. Journal of the American Chemical Society, 141(8), 3613-3622. https://doi.org/10.1021/jacs.8b12872

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title = "Nucleolin is a functional binding protein for salinomycin in neuroblastoma stem cells",

abstract = "The 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.",

author = "Fengfei Wang and Shuang Zhou and Dan Qi and Xiang, {Shi Hua} and Wong, {Eric T.} and Xuejing Wang and Ekokobe Fonkem and Hsieh, {Tze Chen} and Jianhua Yang and Batool Kirmani and Shabb, {John B.} and Wu, {Joseph M.} and Min Wu and Huang, {Jason H.} and Yu, {Wei Hsuan} and Erxi Wu",

note = "Funding Information: We sincerely thank Dr. Bruce Beutler at UT Southwestern Medical Center for his valuable comments and inputs for this manuscript. This study was supported, in part, by grants provided by Baylor Scott & White Health Start-up fund, Plummer funds, the National Center for Research Resources (NCRR; P20 RR020151), National Institute of General Medical Sciences (NIGMS; P20 GM103505, P20GM103442, P20GM113123, P30 GM103332), and National Institute of Allergy and Infectious Diseases (NIAID; R01 AI109317-01A1, R01 AI138203-01) from the National Institutes of Health (NIH). Mass spectrometry was supported by ND INBRE with funding from the National Center for Research Resources (5P20RR016471-12) and the National Institute of General Medical Sciences (8 P20 GM103442-12), NIH. Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

year = "2019",

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doi = "10.1021/jacs.8b12872",

language = "English (US)",

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T1 - Nucleolin is a functional binding protein for salinomycin in neuroblastoma stem cells

AU - Wang, Fengfei

AU - Zhou, Shuang

AU - Qi, Dan

AU - Xiang, Shi Hua

AU - Wong, Eric T.

AU - Wang, Xuejing

AU - Fonkem, Ekokobe

AU - Hsieh, Tze Chen

AU - Yang, Jianhua

AU - Kirmani, Batool

AU - Shabb, John B.

AU - Wu, Joseph M.

AU - Wu, Min

AU - Huang, Jason H.

AU - Yu, Wei Hsuan

AU - Wu, Erxi

N1 - Funding Information: We sincerely thank Dr. Bruce Beutler at UT Southwestern Medical Center for his valuable comments and inputs for this manuscript. This study was supported, in part, by grants provided by Baylor Scott & White Health Start-up fund, Plummer funds, the National Center for Research Resources (NCRR; P20 RR020151), National Institute of General Medical Sciences (NIGMS; P20 GM103505, P20GM103442, P20GM113123, P30 GM103332), and National Institute of Allergy and Infectious Diseases (NIAID; R01 AI109317-01A1, R01 AI138203-01) from the National Institutes of Health (NIH). Mass spectrometry was supported by ND INBRE with funding from the National Center for Research Resources (5P20RR016471-12) and the National Institute of General Medical Sciences (8 P20 GM103442-12), NIH. Publisher Copyright: © 2019 American Chemical Society.

PY - 2019/2/27

Y1 - 2019/2/27

N2 - The 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.

AB - The 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.

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DO - 10.1021/jacs.8b12872

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JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

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ER -

Nucleolin is a functional binding protein for salinomycin in neuroblastoma stem cells

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