4.7 Article

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

期刊

JOURNAL OF TRANSLATIONAL MEDICINE
卷 20, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s12967-022-03361-3

关键词

Gastric cancer; ATF1; Phosphorylation; MMP2

资金

  1. National Natural Science Foundation of China [81772982]
  2. Special Innovation Fund of Department of Education of Guangdong Province [2019KTSCX049]
  3. Disciplinary Construction of Posts for Zhujiang Scholars [4SG21005G]

向作者/读者索取更多资源

The phosphorylation of ATF1 at Thr184 (p-ATF1-T184) plays an important role in the metastasis of gastric cancer (GC) by regulating the expression of Matrix metallopeptidase 2 (MMP2). High expression of p-ATF1-T184 is associated with lymph node metastasis and poor survival in GC.
Background Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2). Methods Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184. Results High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC. Conclusion Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据