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Nucleolin Is a Functional Binding Protein for Salinomycin in Neuroblastoma Stem Cells
Fengfei Wang1,2,3,4, Shuang Zhou1,2,5, Dan Qi1,2
1Department of Neurosurgery , Baylor Scott & White Health , Temple , Texas 78508 , United States.
Journal of the American Chemical Society
|January 29, 2019
Summary
This study identifies nucleolin (NCL) as a salinomycin target, crucial for neuroblastoma (NB) cancer stem cell (CSC) activity. Targeting NCL may offer a new therapeutic strategy and prognostic marker for NB patients.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Neuroblastoma (NB) is a pediatric cancer with a significant unmet need for effective therapies.
- Anticancer stem cells (CSCs) are implicated in tumor recurrence and treatment resistance.
- Salinomycin shows promise as a CSC-targeting agent, but its precise molecular targets remain largely undefined.
Purpose of the Study:
- To identify the functional binding target of salinomycin in neuroblastoma cancer stem cells (CSCs).
- To elucidate the role of this target in regulating CSC activity and therapeutic response.
- To evaluate the potential of this target as a prognostic biomarker for neuroblastoma.
Main Methods:
- Integrated molecular biology strategies were employed.
- Identification of salinomycin-binding targets using biochemical and cellular assays.
- Analysis of nucleolin (NCL) expression and its correlation with patient survival in neuroblastoma (NB) cohorts.
- Investigation of NCL's role in regulating CD34 expression and NB CSC activity.
Main Results:
- Nucleolin (NCL) was identified as a likely functional binding target of salinomycin.
- Salinomycin suppresses NB CD34 expression and reduces CD34+ CSCs in an NCL-dependent manner.
- NCL regulates the interaction between NCL and the CD34 promoter, impacting CSC activity.
- Elevated NCL expression in NB tumors correlates with poorer patient survival.
Conclusions:
- Nucleolin (NCL) is a novel functional salinomycin-binding target critical for neuroblastoma (NB) CSC regulation.
- NCL represents a potential prognostic marker for NB therapy.
- Targeting the NCL-salinomycin interaction could offer a new therapeutic avenue for neuroblastoma.
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