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.
Keywords:
RASSF8; esophageal cancer; lymphangiogenesis; tumor metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Animals
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Blotting, Western
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Carcinoma, Squamous Cell / mortality
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Carcinoma, Squamous Cell / pathology*
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Cell Movement / genetics
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Down-Regulation
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Enzyme-Linked Immunosorbent Assay
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Esophageal Neoplasms / mortality
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Esophageal Neoplasms / pathology*
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Esophageal Squamous Cell Carcinoma
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Female
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Gene Knockdown Techniques
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Genes, Tumor Suppressor / physiology
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Heterografts
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Humans
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Immunohistochemistry
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Kaplan-Meier Estimate
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Lymphangiogenesis / genetics*
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Lymphatic Metastasis / genetics*
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Lymphatic Metastasis / pathology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Middle Aged
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Neoplasm Invasiveness / genetics*
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Prognosis
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Real-Time Polymerase Chain Reaction
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Transfection
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Tumor Suppressor Proteins / biosynthesis*
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Vascular Endothelial Growth Factor C / metabolism
Substances
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RASSF8 protein, human
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Tumor Suppressor Proteins
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Vascular Endothelial Growth Factor C