2. Academic Validation
  3. Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression in blood vessel endothelial cells

Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression in blood vessel endothelial cells

  • J Cell Biochem. 2019 Feb;120(2):1807-1818. doi: 10.1002/jcb.27480.
Jingshu Wang 1 2,  Lina Yang 2,  Fan Liang 2,  Yaping Chen 2,  Gong Yang 1 3 4
Affiliations

Affiliations

  • 1 Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
  • 2 Department of Gynecological Oncology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
  • 3 Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 4 Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, China.
PMID: 30873824 DOI: 10.1002/jcb.27480
Abstract

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/KDR/Flk-1), 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/KDR/Flk-1 or the phosphorylated VEGFR2/KDR/Flk-1. Immunostaining of human ovarian Cancer specimens suggested that endothelial cells of micro-blood vessels displayed strong expression of VEGF-A, c-Myc, VEGFR2/KDR/Flk-1, 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/KDR/Flk-1/VEGF-A overexpression during Cancer development.

Keywords

angiogenesis; integrin alpha x (ITGAX); ovarian cancer; vascular endothelial growth factor‐A (VEGF‐A).

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