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Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma
Kuancan Liu1, Fuan Xie2, Tingting Zhao3
1School of Medicine, Xiamen University or Institute for Laboratory Medicine, 900 Hospital of the Joint Logistics Team, Fuzhou, Fujian 350025, China; Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, China; Fuzhou General Hospital Clinical Medical School, Fujian Medical University, Fuzhou 350025, China.
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.
Insights
Researchers identified peptide 42 as a potential therapy for esophageal squamous cell carcinoma (ESCC). This peptide inhibits SOX2, a protein overexpressed in ESCC, reducing cancer cell growth and spread in laboratory and animal studies.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Esophageal squamous cell carcinoma (ESCC) is a prevalent cancer in developing nations, particularly China, with a high mortality rate due to limited targeted therapies.
- SOX2, a transcription factor, is overexpressed in approximately 30% of ESCC cases, indicating its potential role in cancer progression.
Purpose of the Study:
- To develop and evaluate a novel therapeutic strategy targeting the transcription factor SOX2 in esophageal squamous cell carcinoma.
- To identify and characterize peptide aptamers capable of inhibiting SOX2 function and its downstream effects in ESCC.
Main Methods:
- Establishment of a peptide aptamer library and screening for aptamers that bind and inhibit SOX2.
- In vitro assays to assess the effects of peptide 42 on ESCC cell proliferation, migration, and invasion.
- In vivo studies using xenograft mouse and zebrafish models to evaluate the anti-tumor and anti-metastatic efficacy of peptide 42.
- Analysis of protein level alterations in response to P42 overexpression.
Main Results:
- Peptide aptamer P42 was identified, which binds to and inhibits SOX2 downstream target genes.
- Overexpression or treatment with synthetic peptide 42 significantly inhibited ESCC cell proliferation, migration, and invasion in vitro.
- Peptide 42 treatment demonstrated efficacy in inhibiting tumor growth and metastasis in vivo xenograft models.
- P42 overexpression resulted in changes to key proteins involved in ESCC cell proliferation and migration.
Conclusions:
- Peptide 42 acts as a potent inhibitor of SOX2, effectively reducing ESCC cell proliferation and migration.
- This study presents peptide 42 as a promising therapeutic candidate for esophageal squamous cell carcinoma, offering a targeted approach against SOX2-driven tumors.
