p38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis. Anwar, T., Arellano-Garcia, C., Ropa, J., Chen, Y., Kim, H. S., Yoon, E., Grigsby, S., Basrur, V., Nesvizhskii, A. I., Muntean, A., Gonzalez, M. E., Kidwell, K. M., Nikolovska-Coleska, Z., & Kleer, C. G. Nature communications, 9(1):2801, July, 2018. doi abstract bibtex Overexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. EZH2 has been mainly studied as the catalytic component of the Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how EZH2 drives metastasis despite the low H3K27me3 levels observed in ER- breast cancer is unknown. Here we show that in human invasive carcinomas and distant metastases, cytoplasmic EZH2 phosphorylated at T367 is significantly associated with ER- disease and low H3K27me3 levels. p38-mediated EZH2 phosphorylation at T367 promotes EZH2 cytoplasmic localization and potentiates EZH2 binding to vinculin and other cytoskeletal regulators of cell migration and invasion. Ectopic expression of a phospho-deficient T367A-EZH2 mutant is sufficient to inhibit EZH2 cytoplasmic expression, disrupt binding to cytoskeletal regulators, and reduce
@article{anwar_p38-mediated_2018,
title = {p38-mediated phosphorylation at {T}367 induces {EZH}2 cytoplasmic localization to promote breast cancer metastasis.},
volume = {9},
issn = {2041-1723 2041-1723},
doi = {10.1038/s41467-018-05078-8},
abstract = {Overexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. EZH2 has been mainly studied as the catalytic component of the Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how EZH2 drives metastasis despite the low H3K27me3 levels observed in ER- breast cancer is unknown. Here we show that in human invasive carcinomas and distant metastases, cytoplasmic EZH2 phosphorylated at T367 is significantly associated with ER- disease and low H3K27me3 levels. p38-mediated EZH2 phosphorylation at T367 promotes EZH2 cytoplasmic localization and potentiates EZH2 binding to vinculin and other cytoskeletal regulators of cell migration and invasion. Ectopic expression of a phospho-deficient T367A-EZH2 mutant is sufficient to inhibit EZH2 cytoplasmic expression, disrupt binding to cytoskeletal regulators, and reduce},
language = {eng},
number = {1},
journal = {Nature communications},
author = {Anwar, Talha and Arellano-Garcia, Caroline and Ropa, James and Chen, Yu-Chih and Kim, Hong Sun and Yoon, Euisik and Grigsby, Sierrah and Basrur, Venkatesha and Nesvizhskii, Alexey I. and Muntean, Andrew and Gonzalez, Maria E. and Kidwell, Kelley M. and Nikolovska-Coleska, Zaneta and Kleer, Celina G.},
month = jul,
year = {2018},
pmid = {30022044},
pmcid = {PMC6051995},
keywords = {*Gene Expression Regulation, Neoplastic, Animals, Breast Neoplasms/*genetics/mortality/pathology/therapy, Carcinoma, Ductal, Breast/*genetics/mortality/secondary/therapy, Cell Line, Tumor, Cell Movement, Enhancer of Zeste Homolog 2 Protein/antagonists \& inhibitors/*genetics/metabolism, Estrogen Receptor alpha/genetics/metabolism, Female, Heterografts, Histones/genetics/metabolism, Humans, Lung Neoplasms/*genetics/mortality/secondary/therapy, Mice, Mice, SCID, Phosphorylation, Polycomb Repressive Complex 2/genetics/metabolism, RNA, Small Interfering/genetics/metabolism, Survival Analysis, Threonine, p38 Mitogen-Activated Protein Kinases/antagonists \& inhibitors/*genetics/metabolism},
pages = {2801}
}
Downloads: 0
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