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Tumour-associated macrophages enhance breast cancer malignancy via inducing ZEB1-mediated DNMT1 transcriptional activation.


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.

SUBMITTER: Li Z 

PROVIDER: S-EPMC9587673 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Tumour-associated macrophages enhance breast cancer malignancy via inducing ZEB1-mediated DNMT1 transcriptional activation.

Li Zhongwei Z   Wang Pengfei P   Cui Wenjie W   Yong Hongmei H   Wang Diandian D   Zhao Tiesuo T   Wang Wenwen W   Shi Ming M   Zheng Junnian J   Bai Jin J  

Cell & bioscience 20221022 1


<h4>Background</h4>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.<h4>Results</h4>In this study, we demonstrate that DNMT1 is overexpressed in breast cancer and that DNMT1 promotes breast cancer tumorigenesis and metas  ...[more]

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