Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis
Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Usi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714000837 |
| _version_ | 1828910049637957632 |
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| author | Jian Cao Zongzhi Liu William K.C. Cheung Minghui Zhao Sophia Y. Chen Siew Wee Chan Carmen J. Booth Don X. Nguyen Qin Yan |
| author_facet | Jian Cao Zongzhi Liu William K.C. Cheung Minghui Zhao Sophia Y. Chen Siew Wee Chan Carmen J. Booth Don X. Nguyen Qin Yan |
| author_sort | Jian Cao |
| collection | DOAJ |
| description | Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis. |
| first_indexed | 2024-12-13T18:37:29Z |
| format | Article |
| id | doaj.art-33c18d24ae6e4096b51b0f000f5d5165 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T18:37:29Z |
| publishDate | 2014-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-33c18d24ae6e4096b51b0f000f5d51652022-12-21T23:35:19ZengElsevierCell Reports2211-12472014-03-016586887710.1016/j.celrep.2014.02.004Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and MetastasisJian Cao0Zongzhi Liu1William K.C. Cheung2Minghui Zhao3Sophia Y. Chen4Siew Wee Chan5Carmen J. Booth6Don X. Nguyen7Qin Yan8Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USACancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, SingaporeSection of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USAMetastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis.http://www.sciencedirect.com/science/article/pii/S2211124714000837 |
| spellingShingle | Jian Cao Zongzhi Liu William K.C. Cheung Minghui Zhao Sophia Y. Chen Siew Wee Chan Carmen J. Booth Don X. Nguyen Qin Yan Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis Cell Reports |
| title | Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis |
| title_full | Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis |
| title_fullStr | Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis |
| title_full_unstemmed | Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis |
| title_short | Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis |
| title_sort | histone demethylase rbp2 is critical for breast cancer progression and metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714000837 |
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