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Transcriptional factor OCT4 promotes esophageal cancer metastasis by inducing epithelial-mesenchymal transition through VEGF-C/VEGFR-3 signaling pathway

Chunguang Li, Maoling Zhu, Xiaoli Lou, Chunying Liu, Hezhong Chen, Xuejing Lin, Weidan Ji, Zhigang Li and Changqing Su _

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Oncotarget. 2017; 8:71933-71945. https://doi.org/10.18632/oncotarget.18035

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Abstract

Chunguang Li1,2,*, Maoling Zhu3,*, Xiaoli Lou1,*, Chunying Liu2, Hezhong Chen1, Xuejing Lin2, Weidan Ji2, Zhigang Li4 and Changqing Su2

1Department of Thoracic Surgery and Reconstructive Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China

2Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200433, China

3Department of Gastroenterology, Shanghai Yangpu Hospital, Tongji University, Shanghai 200090, China

4Department of Thoracic Surgery, Shanghai Chest Hospital Esophageal Disease Center, Shanghai Jiao-Tong University, Shanghai 200030, China

*These authors contributed equally to this work

Correspondence to:

Changqing Su, email: [email protected]

Zhigang Li, email: [email protected]

Keywords: esophageal carcinoma, epithelial-mesenchymal transition, octamer-binding transcription factor 4, metastasis, signaling

Received: March 28, 2017     Accepted: May 10, 2017     Published: May 20, 2017

ABSTRACT

The octamer-binding transcription factor 4 (OCT4) can promote cancer proliferation and metastasis. Esophageal carcinoma (ECC) harbors different quantities of OCT4-positive cancer cells. These cells are highly malignant and prone to metastasis; however, the mechanism remains unknown. In this study, we found that OCT4 enhances vascular endothelial growth factor C (VEGF-C) promoter activity to promote VEGF-C expression and activates VEGF receptor 3 (VEGFR-3) in ECC cells, thereby inducing cancer cell epithelial-mesenchymal transition (EMT). Studies using xenograft models showed that OCT4 promoted xenograft growth and intraperitoneal implantation metastasis of ECC cells. Downregulation of OCT4 expression could inhibit cancer metastasis. OCT4- and VEGF-C-positive ECC presented more malignant biological behaviors and the corresponding patients exhibited a poor prognosis. The study confirmed that the OCT4/VEGF-C/VEGFR-3/EMT signaling plays a role in the progression of ECC. Understanding of how OCT4 regulates EMT and how ECC metastasis occurs will provide useful targets for the biological treatment of ECC.


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