AI Article Synopsis
- DNMT1 is highly expressed in breast cancer and is linked to tumor growth and spreading (metastasis), but its mechanism of action is not fully understood.
- The study found that the expression of DNMT1 is activated by ZEB1, which works through a specific pathway involving P300 and acetylation, and that tumor-associated macrophages (TAMs) enhance DNMT1 levels via an IL-6-related signaling axis.
- The research concludes that DNMT1 is crucial for breast cancer metastasis facilitated by TAMs, suggesting that Decitabine, a well-known DNA methylation inhibitor, could be an effective treatment option.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587673 | PMC |
| http://dx.doi.org/10.1186/s13578-022-00913-4 | DOI Listing |
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