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Amplification of transglutaminase 2 enhances tumor-promoting inflammation in gastric cancers

Cited 19 time in Web of Science Cited 21 time in Scopus
Authors

Cho, Sung Yup; Oh, Yumi; Jeong, Eui Man; Park, Sanghui; Lee, Dakeun; Wang, Xiaorui; Zeng, Qiqi; Qin, Hongyu; Hu, Fang; Gong, Hui; Liu, Xi; Zhang, Guanjun; Na, Deukchae; Lee, Jieun; Chae, Jeesoo; Suh, Yun-Suhk; Kong, Seong-Ho; Lee, Hyuk Joon; Kim, Jong Il; Park, Hansoo; Zhang, Chengsheng; Yang, Han Kwang; Lee, Charles

Issue Date
2020-05
Publisher
생화학분자생물학회
Citation
Experimental and Molecular Medicine, Vol.52 No.5, pp.854-864
Abstract
Stomach cancer: Enzyme promotes problematic inflammation An enzyme linked to harmful inflammation that promotes tumor growth could be a target for stomach cancer treatment. The expression of the enzyme transglutaminase 2 (TGM2) has been shown to increase in several types of cancer, but its precise role has been unclear. Sung-Yup Cho at Seoul National University College of Medicine, Korea and co-workers measured copy numbers and expression levels of TGM2 in gastric cancer cell lines and in tissue samples from patients undergoing gastrectomy. They found that higher levels of TGM2 were closely associated with increases in various genes that promote the recruitment and activity of tumor-associated macrophages, malfunctioning white blood cells that drive tumor-promoting inflammation. In addition, stomach cancer patients with higher expression of TGM2 had poorer prognoses, indicating the potential therapeutic value of targeting this enzyme. Tumor-promoting inflammation is a hallmark of cancer and is highly associated with tumor progression, angiogenesis, and metastasis. Tumor-associated macrophages (TAMs) are major drivers of tumor-promoting inflammation, but due to the complexity of the tumor microenvironment, the detailed regulatory mechanisms are still under investigation. Here, we investigated a novel role for transglutaminase 2 (TGM2) in the development of tumor-promoting inflammation and recruitment of TAMs to gastric cancer (GC) tissues. When estimated by array comparative genomic hybridization and droplet digital PCR, the copy numbers of the TGM2 gene were amplified in 13.6% (14/103) of GC patients and positively associated with TGM2 expression. Gene set enrichment analysis of expression microarray data for GC samples with high or low TGM2 expression showed that increased TGM2 expression was associated with tumor-promoting inflammation in GC. In addition, the expression of TGM2 was correlated with the expression of markers for macrophages, neutrophils, blood vessels, and lymphatic vessels. Overexpression of TGM2 in GC cells augmented the IL-1 beta-induced secretion of macrophage-recruiting chemokines and NF-kappa B activation. TGM2 protein levels were associated with the expression levels of the macrophage marker CD163 in human GC tissue samples. Moreover, GC patients with high expression of TGM2 had a worse prognosis than those with low expression of TGM2. These results suggest TGM2 as a novel regulator of the tumor microenvironment of GC and provide a promising target for constraining tumor-promoting inflammation.
ISSN
1226-3613
URI
https://hdl.handle.net/10371/202744
DOI
https://doi.org/10.1038/s12276-020-0444-7
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  • College of Medicine
Research Area Cancer genomics, Drug resistance, Targeted therapeutics

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