Su Jen-Liang, Yang Pan-Chyr, Shih Jin-Yuan, Yang Ching-Yao, Wei Lin-Hung, Hsieh Chang-Yao, Chou Chia-Hung, Jeng Yung-Ming, Wang Ming-Yang, Chang King-Jen, Hung Mien-Chie, Kuo Min-Liang
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Cancer Cell. 2006 Mar;9(3):209-23. doi: 10.1016/j.ccr.2006.02.018.
Flt-4, a VEGF receptor, is activated by its specific ligand, VEGF-C. The resultant signaling pathway promotes angiogenesis and/or lymphangiogenesis. This report provides evidence that the VEGF-C/Flt-4 axis enhances cancer cell mobility and invasiveness and contributes to the promotion of cancer cell metastasis. VEGF-C/Flt-4-mediated invasion and metastasis of cancer cells were found to require upregulation of the neural cell adhesion molecule contactin-1 through activation of the Src-p38 MAPK-C/EBP-dependent pathway. Examination of tumor tissues from various types of cancers revealed high levels of Flt-4 and VEGF-C expression that correlated closely with clinical metastasis and patient survival. The VEGF-C/Flt-4 axis, through upregulation of contactin-1, may regulate the invasive capacity in different types of cancer cells.
Flt-4是一种血管内皮生长因子（VEGF）受体，可被其特异性配体VEGF-C激活。由此产生的信号通路促进血管生成和/或淋巴管生成。本报告提供的证据表明，VEGF-C/Flt-4轴增强癌细胞的迁移和侵袭能力，并促进癌细胞转移。研究发现，VEGF-C/Flt-4介导的癌细胞侵袭和转移需要通过激活Src-p38丝裂原活化蛋白激酶（MAPK）-C/EB（增强子结合蛋白）依赖性途径上调神经细胞黏附分子contactin-1。对各种癌症的肿瘤组织进行检查发现，Flt-4和VEGF-C的高表达水平与临床转移和患者生存率密切相关。VEGF-C/Flt-4轴可能通过上调contactin-1来调节不同类型癌细胞的侵袭能力。
