RASSF8 downregulation promotes lymphangiogenesis and metastasis in esophageal squamous cell carcinoma

RASSF8 下调促进食管鳞状细胞癌淋巴管生成和转移

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作者:Lan Zhang, Jian-Hua Wang, Rong-Xin Liang, Shu-Ting Huang, Jing Xu, Lin-Jing Yuan, Long Huang, Yun Zhou, Xing-Juan Yu, Shao-Yun Wu, Rong-Zhen Luo, Jing-Ping Yun, Wei-Hua Jia, Min Zheng

Abstract

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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