PMID:30873824

Citation	Wang, J, Yang, L, Liang, F, Chen, Y and Yang, G (2019) Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression in blood vessel endothelial cells. J. Cell. Biochem. 120:1807-1818
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), 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.
Links	PubMed Online version:10.1002/jcb.27480
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:MYC	enables	GO:0001046: core promoter sequence-specific DNA binding	ECO:0000314: direct assay evidence used in manual assertion		F	has_input:(UniProtKB:P15692) occurs_in:(CL:0002618)	Seeded From UniProt	complete
HUMAN:ITAX	involved_in	GO:0010628: positive regulation of gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P	has_input:(UniProtKB:P15692) regulates_o_occurs_in:(CL:0002618)|has_input(UniProtKB:P27986) regulates_o_occurs_in:(CL:0002618)|has_input(UniProtKB:P31749) regulates_o_occurs_in:(CL:0002618)|has_input(UniProtKB:P01106) regulates_o_occurs_in:(CL:0002618)|has_input(UniProtKB:P35968) regulates_o_occurs_in:(CL:0002618)|has_input(UniProtKB:P61073) regulates_o_occurs_in:(CL:0002618)	Seeded From UniProt	complete
HUMAN:ITAX	involved_in	GO:0030335: positive regulation of cell migration	ECO:0000315: mutant phenotype evidence used in manual assertion		P	regulates_o_occurs_in:(CL:0002618)	Seeded From UniProt	complete
HUMAN:ITAX	enables	GO:0030971: receptor tyrosine kinase binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P35968	F		Seeded From UniProt	complete
HUMAN:ITAX	involved_in	GO:0008284: positive regulation of cell population proliferation	ECO:0000315: mutant phenotype evidence used in manual assertion		P	regulates_o_occurs_in:(CL:0002618)	Seeded From UniProt	complete
HUMAN:ITAX	involved_in	GO:0045766: positive regulation of angiogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P	regulates_o_occurs_in:(UBERON:0005335)	Seeded From UniProt	complete
HUMAN:ITAX	involved_in	GO:1905956: positive regulation of endothelial tube morphogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P	regulates_o_occurs_in:(CL:0002618)	Seeded From UniProt	complete
HUMAN:MYC	enables	GO:0001047: core promoter binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P15692	F		Seeded From UniProt	complete
HUMAN:VGFR2	enables	GO:0005178: integrin binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P20702	F		Seeded From UniProt	complete

References

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