RASSF8 downregulation promotes lymphangiogenesis and metastasis in esophageal squamous cell carcinoma
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Lan Zhang1,3,4,*, Jian-Hua Wang5,*, Rong-Xin Liang5,*, Shu-Ting Huang1,3,4, Jing Xu3,4, Lin-Jing Yuan1,3,4, Long Huang6, Yun Zhou1,3,4, Xing-Juan Yu3,4, Shao-Yun Wu3,4, Rong-Zhen Luo2,4, Jing-Ping Yun1,2,3, Wei-Hua Jia3,4 and Min Zheng1,3,4
1 Department of Gynecology, Guangzhou, P. R. China
2 Department of Pathology, Sun Yat-Sen University Cancer Center; Guangzhou, P. R. China
3 State Key Laboratory of Oncology in South China, Guangzhou, P. R. China
4 Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
5 Cardiovascular Department, Second People’s Hospital of Guangdong Province, Guangzhou, P. R. China
6 Department of Oncology, The Second Affiliated Hospital, Nanchang University, Nanchang, P. R. China
* These authors have contributed equally to this work
Min Zheng, email:
Jian-Hua Wang, email:
Keywords: tumor metastasis; RASSF8; lymphangiogenesis; esophageal cancer
Received: July 08, 2015 Accepted: September 05, 2015 Published: September 30, 2015
Lymphatic vessels are the major routes of human esophageal squamous cell carcinoma (ESCC) metastasis. Tumor cells secrete pro-lymphangiogenic factors to induce new lymphatic vessels, promoting lymph node metastasis. In this study, we show that RAS association domain family 8 (RASSF8) expression in ESCC clinical samples was inversely correlated with lymph node metastasis and patients survival. Tumor cells with low RASSF8 expression had higher apparent migratory ability, and promoted and lymphangiogenesis both in vitro and in vivo. RASSF8 downregulation enhanced VEGF-C expression and caused subcellular redistribution of p65 in ESCC. Our results show that RASSF8 acts as a tumor suppressor in ESCC and is a potential therapeutic target for preventing lymph node metastasis.
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