Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma.
Animals
Antineoplastic Agents
/ pharmacology
Aptamers, Peptide
/ chemistry
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
Humans
Mice
Molecular Targeted Therapy
Prognosis
Protein Binding
SELEX Aptamer Technique
SOXB1 Transcription Factors
/ antagonists & inhibitors
Xenograft Model Antitumor Assays
Zebrafish
SOX2
drug screen
esophageal squamous cell carcinoma
peptide
peptide aptamers
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
04 03 2020
04 03 2020
Historique:
received:
07
07
2019
revised:
28
12
2019
accepted:
02
01
2020
pubmed:
29
1
2020
medline:
29
12
2020
entrez:
29
1
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31991109
pii: S1525-0016(20)30036-8
doi: 10.1016/j.ymthe.2020.01.012
pmc: PMC7054732
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Aptamers, Peptide
0
Biomarkers, Tumor
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
901-913Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK100342
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA138833
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206564
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120650
Pays : United States
Organisme : BLRD VA
ID : I01 BX002115
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113144
Pays : United States
Informations de copyright
Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
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