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Cancer Cell. 2006 Mar;9(3):209-23.

The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells.

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  • 1Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

Erratum in

  • Cancer Cell. 2007 Feb;11(2):207.
  • Cancer Cell. 2008 Sep 9;14(3):274-7.


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.

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