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Novel peptide GX1 inhibits angiogenesis by specifically binding to transglutaminase-2 in the tumorous endothelial cells of gastric cancer
- Source :
- Cell Death and Disease, Vol 9, Iss 6, Pp 1-16 (2018), Cell Death & Disease
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
Abstract
- The clinical application of GX1, an optimal gastric cancer (GC) targeting peptide, is greatly limited because its receptor in the GC vasculature is unknown. In this study, we screened the candidate receptor of GX1, transglutaminase-2(TGM2), by co-immunoprecipitation (co-IP) combined with mass spectrometry. We found that TGM2 was up-regulated in GC vascular endothelial cells and that GX1 receptor expression was suppressed correspondingly after TGM2 downregulation. A highly consistent co-localization of GX1 receptor and TGM2 was detected at both the cellular and tissue levels. High TGM2 expression was evident in GC tissues from patients with poor prognosis. After TGM2 downregulation, the GX1-mediated inhibition of proliferation and migration and the induction of the apoptosis of GC vascular endothelial cells were weakened or even reversed. Finally, we observed that GX1 could inhibit the GTP-binding activity of TGM2 by reducing its intracellular distribution and downregulating its downstream molecular targets (nuclear factor-kappa B, NF-κB; hypoxia-inducible factor 1-α, HIF1α) in GC vascular endothelial cells. Our study confirms that peptide GX1 can inhibit angiogenesis by directly binding to TGM2, subsequently reducing the GTP-binding activity of TGM2 and thereby suppressing its downstream pathway(NF-κB/HIF1α). Our conclusions suggest that GX1/TGM2 may provide a new target for the diagnosis and treatment of GC.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Tissue transglutaminase
Angiogenesis
Receptor expression
Immunology
Down-Regulation
Apoptosis
Peptides, Cyclic
Article
Neovascularization
03 medical and health sciences
Cellular and Molecular Neuroscience
Downregulation and upregulation
Cell Movement
GTP-Binding Proteins
Stomach Neoplasms
Cell Line, Tumor
Human Umbilical Vein Endothelial Cells
medicine
Humans
Protein Glutamine gamma Glutamyltransferase 2
lcsh:QH573-671
Receptor
Cell Proliferation
Transglutaminases
Neovascularization, Pathologic
biology
Chemistry
lcsh:Cytology
Endothelial Cells
Cell Biology
Middle Aged
Prognosis
Up-Regulation
030104 developmental biology
Cell culture
biology.protein
Cancer research
Female
medicine.symptom
Oligopeptides
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 9
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....8c99234d2c95dc7ae40652d14dd8a2e5