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Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling–mediated VEGFR2/VEGF‐A overexpression in blood vessel endothelial cells
Author(s) -
Wang Jingshu,
Yang Lina,
Liang Fan,
Chen Yaping,
Yang Gong
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27480
Subject(s) - angiogenesis , cancer research , pi3k/akt/mtor pathway , protein kinase b , vascular endothelial growth factor , kinase insert domain receptor , integrin , vascular endothelial growth factor a , biology , umbilical vein , microbiology and biotechnology , signal transduction , chemistry , receptor , vegf receptors , biochemistry , in vitro
Integrin alpha x (ITGAX), a member of the integrin family, usually serves as a receptor of the extracellular matrix. Recently, accumulating evidence suggests that ITGAX may be involved in angiogenesis in dendritic cells. Herein, we report a direct role of ITGAX in angiogenesis during tumor development. Overexpression of ITGAX in human umbilical vein endothelial cells (HUVECs) enhanced their proliferation, migration, and tube formation and promoted xenograft ovarian tumor angiogenesis and growth. Further study showed that overexpression of ITGAX activated the PI3k/Akt pathway, leading to the enhanced expression of c‐Myc, vascular endothelial growth factor‐A (VEGF‐A), and VEGF receptor 2 (VEGFR2), whereas, the treatment of cells with PI3K inhibitor diminished these effects. Besides, c‐Myc was observed to bind to the VEGF‐A promoter. By Co‐Immunoprecipitation (Co‐IP) assay, we manifested the interaction between ITGAX and VEGFR2 or the phosphorylated VEGFR2. Immunostaining of human ovarian cancer specimens suggested that endothelial cells of micro–blood vessels displayed strong expression of VEGF‐A, c‐Myc, VEGFR2, and the PI3K signaling molecules. Also, overexpression of ITGAX in HUVECs could stimulate the spheroid formation of ovarian cancer cells. Our study uncovered that ITGAX stimulates angiogenesis through the PI3K/Akt signaling–mediated VEGFR2/VEGF‐A overexpression during cancer development.