Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer

Li, Tong; Cao, Huiyuan; Wu, Sa; Zhong, Peimin; Ding, Jie; Wang, Jing; Wang, Fangfang; He, Zhiwei; Huang, Guoliang

doi:10.1186/s12967-022-03361-3

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…A zinc-dependent metalloproteinase called MMP2 has been connected to angiogenesis and cancer 16 . Higher levels of the protein MMP2 were shown to be associated with better survival in Li's cohort of patients with gastric cancer 17 . MMP2, also referred to as type IV collagenase, is released in the form of an inactive proenzyme that, when activated by hydrolysis, may break down gelatin and other proteins in the extracellular matrix, which is crucial for tumor invasion and metastasis 18 .…”

Section: Discussionmentioning

confidence: 95%

Identification and validation of a T cell marker gene-based signature to predict prognosis and immunotherapy response in gastric cancer

Zhong,

Pan,

Gao

et al. 2023

Sci Rep

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Although the role of T cells in tumor immunity and modulation of the tumor microenvironment (TME) has been extensively studied, their precise involvement in gastric adenocarcinoma remains inadequately explored. In this work, we analyzed the single-cell RNA sequencing data set in GSE183904 and identified 322 T cell marker genes using the “FindAllMarkers” method of the R package “Seurat”. STAD patients in the TCGA database were divided into high-risk and low-risk categories based on risk scores. The five-gene prediction signature based on T cell marker genes can predict the prognosis of gastric cancer patients with high accuracy. In the training cohort, the areas under the receiver operating characteristic (ROC) curve were 0.667, 0.73, and 0.818 at 1, 3, and 5 years. External validation of the predictive signature was also performed using multiple clinical subgroups and GEO cohorts. To help with practical application, a diagnostic model was created that shows values of 0.732, 0.752, and 0.816 for the relevant areas under the ROC curve at 1, 3, and 5 years. The T cell marker genes identified in this study may serve as potential therapeutic targets, and the developed predictive signatures and nomograms may aid in the clinical management of gastric cancer.

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Section: Discussionmentioning

confidence: 95%

Identification and validation of a T cell marker gene-based signature to predict prognosis and immunotherapy response in gastric cancer

Zhong,

Pan,

Gao

et al. 2023

Sci Rep

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“…MMPs can degrade the basement membrane and extracellular matrix, which are closely related to tumor growth, invasion, and metastasis 28 . Research has shown that the activity and expression level of MMPs such as MMP2, MMP3, MMP7, and MMP9 are increased in gastric cancer patients, which can reduce the survival period of gastric cancer patients, promote the metastasis and recurrence of cancer, and is associated with poor prognosis of gastric cancer [29][30][31] . MMP7 is secreted by tumor cells themselves, which is better as a marker of tumor progression compared to other members of the MMPs family.…”

Section: Discussionmentioning

confidence: 99%

EGFR and MMP7 are important targets for gastric cancer metastasis

Ding,

Wan,

et al. 2023

Preprint

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The invasion and metastasis of gastric cancer pose frequent clinical challenges following standard treatment. Investigating the molecular mechanisms underpinning gastric cancer invasion and metastasis constitutes a critical research area. This study aims to pinpoint potential target molecules involved in gastric cancer metastasis. After analyzing the TCGA database, we identified overexpression of EGFR and MMP7 in gastric adenocarcinoma, which correlates with unfavorable patient outcomes. Notably, MMP7 expression is closely linked to gastric adenocarcinoma metastasis. Immunohistochemical analysis of clinical gastric adenocarcinoma tissue samples confirmed the association of both EGFR and MMP7 with metastasis, aligning with the findings from bioinformatics analysis. Moreover, our immunohistochemical results revealed a positive correlation between EGFR and MMP7 expression, providing a foundational basis for future endeavors in searching for drug targets to prevent and treat gastric cancer invasion and metastasis.

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“…The down-regulation of ATF1 has been linked to early neuroectoderm differentiation of human embryonic stem cells through SRY-box transcription factor 2 (SOX2) [9]. Simultaneously, ATF1 has been implicated in promoting metastasis and regulating the expression of matrix metalloproteinase 2 (MMP2) in gastric cancer [10]. However, the regulatory mechanism of ATF1 in periodontitis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Upregulated ATF1 Promotes Lipopolysaccharide Induced Inflammatory Response and Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Regulating NF-κB Pathway

Guo,

Yan,

Zhao

2024

Discovery Medicine

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Background: Periodontitis is a chronic inflammatory disease resulting from bacterial plaque infection. While the involvement of activating transcription factor 1 (ATF1) has been extensively explored in various human diseases, its specific role in periodontitis remains unclear. This study aims to elucidate the expression and biological function of ATF1 in the context of periodontitis. Methods: Primary human periodontal ligament cells (hPDLCs) were procured from clinical samples and subsequently characterized. Following treatment with P. gingivalis lipopolysaccharide (LPS, 10 µg/mL), hPDLCs underwent transfection with either ATF1 vector or siRNA. The expression levels of ATF1 in LPS-treated hPDLCs or transfected cells were evaluated through realtime quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Inflammatory factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β), were quantified using Enzymelinked Immunosorbent Assay (ELISA). The assessment of osteogenic proteins, such as runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteoprotegerin (OPG), as well as noncanonical nuclear factor-kappaB (NF-κB) pathway-related proteins (p65, p-p65, IkBα, p-IkBα), was conducted using western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry assays were employed to detect cell viability. Results: LPS induced an inflammatory response and hindered the osteogenic differentiation of hPDLCs (p < 0.05, p < 0.01). Furthermore, ATF1 silencing enhanced cell proliferation and suppressed apoptosis in LPS-stimulated hPDLCs (p < 0.05, p < 0.01). ATF1 silencing not only restrained the inflammatory response but also promoted the osteogenic differentiation of LPSstimulated hPDLCs (p < 0.05, p < 0.01). Importantly, ATF1 silencing effectively blocked the LPS-induced activation of the NF-κB signaling pathway (p < 0.05, p < 0.01, p < 0.001). Conclusions: ATF1 emerges as a promising treatment option, inhibiting the osteogenic differentiation of hPDLCs and mitigating the inflammatory response by preventing the phosphorylation of the NF-κB signaling pathway.

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Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer

Cited by 7 publications

References 44 publications

Identification and validation of a T cell marker gene-based signature to predict prognosis and immunotherapy response in gastric cancer

Identification and validation of a T cell marker gene-based signature to predict prognosis and immunotherapy response in gastric cancer

EGFR and MMP7 are important targets for gastric cancer metastasis

Upregulated ATF1 Promotes Lipopolysaccharide Induced Inflammatory Response and Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Regulating NF-κB Pathway

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