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Histone deacetylases, Mbd3/NuRD, and Tet2 hydroxylase are crucial regulators of epithelial–mesenchymal plasticity and tumor metastasis

Nihan Kilinc, A and Sugiyama, N and Reddy Kalathur, RK and Antoniadis, H and Birogul, H and Ishay-Ronen, D and George, JT and Levine, H and Kumar Jolly, M and Christofori, G (2020) Histone deacetylases, Mbd3/NuRD, and Tet2 hydroxylase are crucial regulators of epithelial–mesenchymal plasticity and tumor metastasis. In: Oncogene, 39 (7). pp. 1498-1513.

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Official URL: https://doi.org/10.1038/s41388-019-1081-2


An epithelial–mesenchymal transition (EMT) represents a basic morphogenetic process of high cell plasticity underlying embryogenesis, wound healing, cancer metastasis and drug resistance. It involves a profound transcriptional and epigenetic reprogramming of cells. A critical role of epigenetic modifiers and their specific chromatin modifications has been demonstrated during EMT. However, it has remained elusive whether epigenetic control differs between the dynamic cell state transitions of reversible EMT and the fixed differentiation status of irreversible EMT. We have employed varying EMT models of murine breast cancer cells to identify the key players establishing epithelial–mesenchymal cell plasticity during reversible and irreversible EMT. We demonstrate that the Mbd3/NuRD complex and the activities of histone deacetylases (HDACs), and Tet2 hydroxylase play a critical role in keeping cancer cells in a highly metastatic mesenchymal state. Combinatorial interference with their functions leads to mesenchymal–epithelial transition (MET) and efficiently represses metastasis formation by invasive murine and human breast cancer cells in vivo

Item Type: Journal Article
Publication: Oncogene
Publisher: Springer Nature
Additional Information: The copyright for this article belongs to the Springer Nature.
Keywords: histone deacetylase; hydrolase; Mbd3 protein; methyl CpG binding protein; NuRD protein; oxygenase; Tet2 protein; unclassified drug; DNA binding protein; histone deacetylase; MBD3 protein, human; oncoprotein; TET2 protein, human, animal cell; animal experiment; animal model; animal tissue; Article; breast cancer; breast cancer cell line; cell plasticity; controlled study; enzyme activity; epithelial mesenchymal transition; human; human cell; metastasis; mouse; nonhuman; priority journal; protein protein interaction; tumor growth; animal; carcinogenesis; cell proliferation; experimental mammary neoplasm; metabolism; metastasis; pathology; tumor cell line, Animals; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; DNA-Binding Proteins; Epithelial-Mesenchymal Transition; Histone Deacetylases; Humans; Mammary Neoplasms, Experimental; Mi-2 Nucleosome Remodeling and Deacetylase Complex; Mice; Neoplasm Metastasis; Proto-Oncogene Proteins
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 02 Feb 2023 07:05
Last Modified: 02 Feb 2023 07:05
URI: https://eprints.iisc.ac.in/id/eprint/79731

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