期刊
CELL AND BIOSCIENCE
卷 12, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13578-022-00913-4
关键词
DNMT1; ZEB1; Tumour-associated macrophages; Metastasis; Breast cancer
资金
- National Natural Science Foundation of China [82173060]
- Excellent Youth Foundation of Jiangsu Province of China [BK20220119]
- Major Project of University Natural Science Foundation of Jiangsu Province of China [22KJA310006]
- National Postdoctoral Research Funds of China [2019M651971, 2021T140577]
- Graduate Research and Practice Innovation Program of Jiangsu [KYCX21_2689]
- Qinglan Project of Jiangsu
The study found that DNMT1 is overexpressed in breast cancer and promotes tumorigenesis and metastasis by activating its expression through ZEB1 and P300, and increasing its expression through the IL-6-pSTAT3-ZEB1-DNMT1 axis in the tumor microenvironment.
Background DNMT1 has been shown to be highly expressed in a variety of cancers, including breast cancer. However, the mechanism is not very clear. Therefore, we aim to reveal the mechanism of DNMT1 highly express in breast cancer. And we also want to explore the role of DNMT1 in tumour microenvironment promoting breast cancer progression. Results In this study, we demonstrate that DNMT1 is overexpressed in breast cancer and that DNMT1 promotes breast cancer tumorigenesis and metastasis. We discovered that ZEB1 activates DNMT1 expression in breast cancer cells by recruiting P300 binding to the DNMT1 promoter and increasing its acetylation. Moreover, we revealed that tumour-associated macrophages (TAMs) increase DNMT1 expression in breast cancer cells via the IL-6-pSTAT3-ZEB1-DNMT1 axis in the tumour microenvironment. DNMT1 is required for TAM-mediated breast cancer cell migration. In addition, we confirmed that there were positive correlations among CD163 (TAM marker) expression, ZEB1 expression and DNMT1 expression in breast cancer patient tissues. Conclusions Our study indicates that DNMT1 is necessary for TAM-mediated breast cancer metastasis. Decitabine (DAC), as a specific DNA methylation inhibitor and FDA-approved drug, is a bona fide drug for breast cancer treatment.
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。
推荐
暂无数据