Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma.,Molecular Therapy

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Targeting SOX2 Protein with Peptide Aptamers for Therapeutic Gains against Esophageal Squamous Cell Carcinoma.
Molecular Therapy ( IF 12.4 ) Pub Date : 2020-01-15 , DOI: 10.1016/j.ymthe.2020.01.012
Kuancan Liu ₁ , Fuan Xie ₂ , Tingting Zhao ₃ , Rui Zhang ₂ , Anding Gao ₂ , Yunyun Chen ₃ , Haiyan Li ₄ , Shihui Zhang ₅ , Zhangwu Xiao ₆ , Jieping Li ₇ , Xiaoqian Hong ₃ , Lei Shang ₃ , Weifeng Huang ₈ , Junkai Wang ₉ , Wael El-Rifai ₁₀ , Alexander Zaika ₁₀ , Xi Chen ₁₁ , Jianwen Que ₁₂ , Xiaopeng Lan ₂

Affiliation

School 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.
School of Medicine, Xiamen University or Institute for Laboratory Medicine, 900 Hospital of the Joint Logistics Team, Fuzhou, Fujian 350025, China.
School 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.
Department of Pathology, Westechester Medical Center, Valhalla, NY 10595, USA.
School of Life Sciences, Central South University, Changsha, Hunan 410083, China.
Emergency Department, 900 Hospital of the Joint Logistics Team, Fuzhou, Fujian 350002, China.
Department of Clinic Medical Laboratory, General Hospital of Fujian Corps of CAPF, Fuzhou, Fujian 350003, China.
Medical College, China Three Gorges University, Yichang, Hubei 443002, China.
School of Life Science, Xiamen University, Xiamen, Fujian 361102, China.
Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Medical Oncology, 900 Hospital of the Joint Logistics Team or Dongfang Hospital, Fuzhou, Fujian 350025, China.
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.

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.

更新日期：2020-01-15

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