The study of vascular endothelial growth factor receptor 1 (VEGFR1) subcellular localization and its functional implication in carcinogenesis

• Main Authors: Chiu-Ying Peng, 彭秋瑩
• Other Authors: Li-Wha Wu
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/04588294554910446900

碩士 === 國立成功大學 === 分子醫學研究所 === 96 === Vascular endothelial growth factor receptor 1 (VEGFR1) is a receptor tyrosine kinase (RTK) predominantly expressed on the plasma membrane of endothelial cells. Recent studies have shown that VEGFR1 is also expressed in several types of human cancer cells, and its expression correlates with cancer progression and predicts the outcome of cancer patients following cancer treatments. Studies in chronic B cell leukemia suggest that VEGFR1 could be internalized from cell membrane and associated with phosphorylated STAT3 in response to VEGF-A stimulation. We hypothesize that VEGFR1 may work in similar fashion like EGFR, which employs activated receptor internalization to act as a transcription mediator in nucleus. We first examined the function of a putative nuclear translocataion signal (NLS) segment within VEGFR1 by site-directed mutagenesis and immunofluorescence (IF) microscopy. Although additional sequence may be required, VEGFR1 indeed harbored a functional NLS segment, in which lysine 954 residue played a dominant role. The nuclear localization of VEGFR1 was in part mediated by its association with importin β1 (impB1), normally required for nuclear transport of proteins. Exogenous VEGF-A, frequently overexpressed in oral cancer cells, had no effect on the subcellular localization of VEGFR1. Knocking down the expression of VEGFR1 decreased the proliferation and migration abilities of oral cancer cells. Nuclear expression of VEGFR1 was also observed in the invasion front of oral cancer specimens. Together, VEGFR1 indeed harbored a functional NLS to enter cell nucleus, the exact function of nuclear VEGFR2 in oral cancer cells and the prognostic value of its expression in nuclei remains to be elucidated.