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Published on: June 9, 2023
FOXK1 promotes hormonally responsive breast carcinogenesis by suppressing apoptosis
Minghui Zhao1, Tingyao Ma2, Zhaohan Zhang1
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Background:
Globally, breast cancer constitutes the predominant malignancy in women. Abnormal regulation of epigenetic factors plays a key role in the development of tumors. Anti-apoptosis is a characteristic of tumor cells. Therefore, exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.
Method:
This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive (ER+) breast cancer. We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions. ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites. To validate the ChIP-seq results, qChIP, western blotting, and quantitative polymerase chain reaction (qPCR) were performed. Through TUNEL assay, cell counting assay, colony formation assay, and the mouse xenograft models, the effect of FOXK1 on breast cancer progression was detected. Finally, by analyzing online databases, the correlation between FOXK1 and the survival of breast cancer patients was examined.
Results:
FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway. Abnormally high expression of FOXK1 prevents the apoptosis of ER+ breast cancer cells in vitro and promotes ER+ breast tumor progression in vivo. Furthermore, the expression of FOXK1 is negatively correlated with the survival of ER+ breast cancer patients.
Conclusion:
FOXK1 promotes ER+ breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+ breast cancer treatment.
Insights
Forkhead box K1 (FOXK1) promotes estrogen receptor-positive breast cancer by inhibiting apoptosis. Targeting FOXK1 may offer a new therapeutic strategy for breast cancer patients.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Breast cancer is a leading malignancy in women, with abnormal epigenetic regulation contributing to tumor development.
- Tumor cells exhibit anti-apoptotic properties, making the study of epigenetic factors regulating apoptosis crucial for understanding cancer pathogenesis and developing targeted therapies.
Purpose of the Study:
- To investigate the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive (ER+) breast cancer.
- To elucidate how FOXK1 influences the apoptosis of ER+ breast cancer cells and its role in tumor progression.
Main Methods:
- Overexpression of FLAG-FOXK1 in MCF-7 cells, mass spectrometry, and Co-immunoprecipitation (Co-IP) to identify interacting proteins.
- Chromatin immunoprecipitation sequencing (ChIP-seq) to map FOXK1 binding sites and transcriptional targets, validated by quantitative ChIP, Western blotting, and qPCR.
- Functional assays including TUNEL, cell counting, colony formation, and mouse xenograft models to assess FOXK1's impact on breast cancer progression.
Main Results:
- FOXK1 interacts with the REST/CoREST complex, leading to transcriptional inhibition of apoptotic pathway genes.
- High FOXK1 expression inhibits apoptosis in ER+ breast cancer cells in vitro and promotes tumor progression in vivo.
- FOXK1 expression is negatively correlated with patient survival in ER+ breast cancer.
Conclusions:
- FOXK1 promotes ER+ breast carcinogenesis by suppressing apoptosis.
- FOXK1 represents a potential therapeutic target for ER+ breast cancer treatment.
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