FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancer
Breast cancer biology varies markedly among patients. Basal-like breast cancer is one of the most challenging subtypes to treat because it lacks effective therapeutic targets. Despite numerous studies on potential targetable molecules in this subtype, few targets have shown promise. However, the pre...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1156111/full |
| _version_ | 1797829944221368320 |
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| author | Kohei Kumegawa Liying Yang Kenichi Miyata Reo Maruyama Reo Maruyama |
| author_facet | Kohei Kumegawa Liying Yang Kenichi Miyata Reo Maruyama Reo Maruyama |
| author_sort | Kohei Kumegawa |
| collection | DOAJ |
| description | Breast cancer biology varies markedly among patients. Basal-like breast cancer is one of the most challenging subtypes to treat because it lacks effective therapeutic targets. Despite numerous studies on potential targetable molecules in this subtype, few targets have shown promise. However, the present study revealed that FOXD1, a transcription factor that functions in both normal development and malignancy, is associated with poor prognosis in basal-like breast cancer. We analyzed publicly available RNA sequencing data and conducted FOXD1-knockdown experiments, finding that FOXD1 maintains gene expression programs that contribute to tumor progression. We first conducted survival analysis of patients grouped via a Gaussian mixture model based on gene expression in basal-like tumors, finding that FOXD1 is a prognostic factor specific to this subtype. Then, our RNA sequencing and chromatin immunoprecipitation sequencing experiments using the basal-like breast cancer cell lines BT549 and Hs578T with FOXD1 knockdown revealed that FOXD1 regulates enhancer–gene programs related to tumor progression. These findings suggest that FOXD1 plays an important role in basal-like breast cancer progression and may represent a promising therapeutic target. |
| first_indexed | 2024-04-09T13:29:20Z |
| format | Article |
| id | doaj.art-24c099bb9fe747feb6446ebf2ebabb66 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T13:29:20Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-24c099bb9fe747feb6446ebf2ebabb662023-05-10T05:13:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.11561111156111FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancerKohei Kumegawa0Liying Yang1Kenichi Miyata2Reo Maruyama3Reo Maruyama4Cancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, JapanProject for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, JapanProject for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, JapanCancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, JapanProject for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, JapanBreast cancer biology varies markedly among patients. Basal-like breast cancer is one of the most challenging subtypes to treat because it lacks effective therapeutic targets. Despite numerous studies on potential targetable molecules in this subtype, few targets have shown promise. However, the present study revealed that FOXD1, a transcription factor that functions in both normal development and malignancy, is associated with poor prognosis in basal-like breast cancer. We analyzed publicly available RNA sequencing data and conducted FOXD1-knockdown experiments, finding that FOXD1 maintains gene expression programs that contribute to tumor progression. We first conducted survival analysis of patients grouped via a Gaussian mixture model based on gene expression in basal-like tumors, finding that FOXD1 is a prognostic factor specific to this subtype. Then, our RNA sequencing and chromatin immunoprecipitation sequencing experiments using the basal-like breast cancer cell lines BT549 and Hs578T with FOXD1 knockdown revealed that FOXD1 regulates enhancer–gene programs related to tumor progression. These findings suggest that FOXD1 plays an important role in basal-like breast cancer progression and may represent a promising therapeutic target.https://www.frontiersin.org/articles/10.3389/fonc.2023.1156111/fullFOXD1TCGAgaussian mixture modelenhancerbasal-like breast cancer |
| spellingShingle | Kohei Kumegawa Liying Yang Kenichi Miyata Reo Maruyama Reo Maruyama FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancer Frontiers in Oncology FOXD1 TCGA gaussian mixture model enhancer basal-like breast cancer |
| title | FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancer |
| title_full | FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancer |
| title_fullStr | FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancer |
| title_full_unstemmed | FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancer |
| title_short | FOXD1 is associated with poor outcome and maintains tumor-promoting enhancer–gene programs in basal-like breast cancer |
| title_sort | foxd1 is associated with poor outcome and maintains tumor promoting enhancer gene programs in basal like breast cancer |
| topic | FOXD1 TCGA gaussian mixture model enhancer basal-like breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1156111/full |
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