title: RASSF8 downregulation promotes lymphangiogenesis and metastasis in esophageal squamous cell carcinoma.
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.
authors.affiliation: Department of Gynecology, Guangzhou, P. R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cardiovascular Department, Second People's Hospital of Guangdong Province, Guangzhou, P. R. China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Cardiovascular Department, Second People's Hospital of Guangdong Province, Guangzhou, P. R. China.
authors.forename: Rong-Xin
authors.initials: RX
authors.lastname: Liang
authors.affiliation: Department of Gynecology, Guangzhou, P. R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Gynecology, Guangzhou, P. R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Lin-Jing
authors.initials: LJ
authors.lastname: Yuan
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Nanchang University, Nanchang, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Gynecology, Guangzhou, P. R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Xing-Juan
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Shao-Yun
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Luo
authors.affiliation: Department of Gynecology, Guangzhou, P. R. China.|Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.affiliation: Department of Gynecology, Guangzhou, P. R. China.|State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor / Q000502:physiology; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: C512680:RASSF8 protein, human; D025521:Tumor Suppressor Proteins; D042582:Vascular Endothelial Growth Factor C
keywords: RASSF8; esophageal cancer; lymphangiogenesis; tumor metastasis