PUBLICATION
Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma
- Authors
- Liu, K., Xie, F., Zhao, T., Zhang, R., Gao, A., Chen, Y., Li, H., Zhang, S., Xiao, Z., Li, J., Hong, X., Shang, L., Huang, W., Wang, J., El-Rifai, W., Zaika, A., Chen, X., Que, J., Lan, X.
- ID
- ZDB-PUB-200129-18
- Date
- 2020
- Source
- Molecular therapy : the journal of the American Society of Gene Therapy 28(3): 901-913 (Journal)
- Registered Authors
- Zhang, Rui
- Keywords
- SOX2, drug screen, esophageal squamous cell carcinoma, peptide, peptide aptamers
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology*
- Aptamers, Peptide/chemistry
- Aptamers, Peptide/metabolism
- Aptamers, Peptide/pharmacology*
- Biomarkers, Tumor
- Cell Line, Tumor
- Cell Movement/genetics
- Cell Proliferation/drug effects
- Disease Models, Animal
- Drug Screening Assays, Antitumor
- Esophageal Squamous Cell Carcinoma/drug therapy
- Esophageal Squamous Cell Carcinoma/metabolism
- Esophageal Squamous Cell Carcinoma/mortality
- Humans
- Mice
- Molecular Targeted Therapy
- Prognosis
- Protein Binding
- SELEX Aptamer Technique
- SOXB1 Transcription Factors/antagonists & inhibitors*
- SOXB1 Transcription Factors/metabolism
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 31991109 Full text @ Mol. Ther.
Citation
Liu, K., Xie, F., Zhao, T., Zhang, R., Gao, A., Chen, Y., Li, H., Zhang, S., Xiao, Z., Li, J., Hong, X., Shang, L., Huang, W., Wang, J., El-Rifai, W., Zaika, A., Chen, X., Que, J., Lan, X. (2020) Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy. 28(3):901-913.
Abstract
Esophageal squamous cell carcinoma (ESCC) is a predominant cancer type in developing countries such as China, where ESCC accounts for approximately 90% of esophageal malignancies. Lacking effective and targeted therapy contributes to the poor 5-year survival rate. Recent studies showed that about 30% of ESCC cases have high levels of SOX2. Herein, we aim to target this transcription factor with aptamer. We established a peptide aptamer library and then performed an unbiased screening to identify several peptide aptamers including P42 that can bind and inhibit SOX2 downstream target genes. We further found that P42 overexpression or incubation with a synthetic peptide 42 inhibited the proliferation, migration, and invasion of ESCC cells. Moreover, peptide 42 treatment inhibited the growth and metastasis of ESCC xenografts in mouse and zebrafish. Further analysis revealed that P42 overexpression led to alternations in the levels of proteins that are important for the proliferation and migration of ESCC cells. Taken together, our study identified the peptide 42 as a key inhibitor of SOX2 function, reducing the proliferation and migration of ESCC cells in vitro and in vivo, and thereby offering a potential therapy against ESCC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping