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

// Chunguang Li 1, 2, * , Maoling Zhu 3, * , Xiaoli Lou 1, * , Chunying Liu 2 , Hezhong Chen 1 , Xuejing Lin 2 , Weidan Ji 2 , Zhigang Li 4 and Changqing Su 2 1 Department of Thoracic Surgery and Reconstructive Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China 2 Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200433, China 3 Department of Gastroenterology, Shanghai Yangpu Hospital, Tongji University, Shanghai 200090, China 4 Department 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: suchangqing@gmail.com Zhigang Li, email: dr_lizhigang@163.com 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.