Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma

Kuancan Liu, Fuan Xie, Tingting Zhao, Rui Zhang, Anding Gao, Yunyun Chen, Haiyan Li, Shihui Zhang, Zhangwu Xiao, Jieping Li, Xiaoqian Hong, Lei Shang, Weifeng Huang, Junkai Wang, Wael El-Rifai, Alexander Zaika, Xi Chen, Jianwen Que, Xiaopeng Lan

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)901-913
Number of pages13
JournalMolecular Therapy
Volume28
Issue number3
DOIs
StatePublished - Mar 4 2020

Keywords

  • SOX2
  • drug screen
  • esophageal squamous cell carcinoma
  • peptide
  • peptide aptamers

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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