TNF-α secreted from macrophages increases the expression of prometastatic integrin αV in gastric cancer

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Title
TNF-α secreted from macrophages increases the expression of prometastatic integrin αV in gastric cancer
Author(s)
Mi Aie Hwang; Misun Won; Joo-Young ImMi-Jung Kang; D H Kweon; Bo Kyung Kim
Bibliographic Citation
International Journal of Molecular Sciences, vol. 24, no. 1, pp. 376-376
Publication Year
2023
Abstract
The tumor microenvironment comprising blood vessels, fibroblasts, immune cells, and the extracellular matrix surrounding cancer cells, has recently been targeted for research in cancer therapy. We aimed to investigate the effect of macrophages on the invasive ability of gastric cancer cells, and studied their potential mechanism. In transcriptome analysis, integrin αV was identified as a gene increased in AGS cells cocultured with RAW264.7 cells. AGS cells cocultured with RAW264.7 cells displayed increased adhesion to the extracellular matrix and greater invasiveness compared with AGS cells cultured alone. This increased invasion of AGS cells cocultured with RAW264.7 cells was inhibited by integrin αV knockdown. In addition, the increase in integrin αV expression induced by tumor necrosis factor-α (TNF-α) or by coculture with RAW264.7 cells was inhibited by TNF receptor 1 (TNFR1) knockdown. The increase in integrin αV expression induced by TNF-α was inhibited by both Mitogen-activated protein kinase (MEK) inhibitor and VGLL1 S84 peptide treatment. Finally, transcription of integrin αV was shown to be regulated through the binding of VGLL1 and TEAD4 to the promoter of integrin αV. In conclusion, our study demonstrated that TNFR1?ERK?VGLL1 signaling activated by TNF-α secreted from RAW264.7 cells increased integrin αV expression, thereby increasing the adhesion and invasive ability of gastric cancer cells.
Keyword
Gastric cancerMacrophageTNF-αIntegrin αV
ISSN
1661-6596
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms24010376
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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