Title | Dynamic Incorporation of Histone H3 Variants into Chromatin Is Essential for Acquisition of Aggressive Traits and Metastatic Colonization. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Gomes, Ana P., Ilter Didem, Low Vivien, Rosenzweig Adam, Shen Zih-Jie, Schild Tanya, Rivas MartĂn A., Er Ekrem E., McNally Dylan R., Mutvei Anders P., Han Julie, Ou Yi-Hung, Cavaliere Paola, Mullarky Edouard, Nagiec Michal, Shin Sejeong, Yoon Sang-Oh, Dephoure Noah, MassaguĂ© Joan, Melnick Ari M., Cantley Lewis C., Tyler Jessica K., and Blenis John |
Journal | Cancer Cell |
Volume | 36 |
Issue | 4 |
Pagination | 402-417.e13 |
Date Published | 2019 Oct 14 |
ISSN | 1878-3686 |
Keywords | Animals, Carcinogenesis, Carcinoma, Cell Line, Tumor, Chromatin, Chromatin Assembly Factor-1, Disease Progression, Epigenesis, Genetic, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Histones, Humans, Male, Mice, Neoplasm Metastasis, Promoter Regions, Genetic, RNA-Seq, Transcription Factors, Xenograft Model Antitumor Assays |
Abstract | <p>Metastasis is the leading cause of cancer mortality. Chromatin remodeling provides the foundation for the cellular reprogramming necessary to drive metastasis. However, little is known about the nature of this remodeling and its regulation. Here, we show that metastasis-inducing pathways regulate histone chaperones to reduce canonical histone incorporation into chromatin, triggering deposition of H3.3 variant at the promoters of poor-prognosis genes and metastasis-inducing transcription factors. This specific incorporation of H3.3 into chromatin is both necessary and sufficient for the induction of aggressive traits that allow for metastasis formation. Together, our data clearly show incorporation of histone variant H3.3 into chromatin as a major regulator of cell fate during tumorigenesis, and histone chaperones as valuable therapeutic targets for invasive carcinomas.</p> |
DOI | 10.1016/j.ccell.2019.08.006 |
Alternate Journal | Cancer Cell |
PubMed ID | 31564638 |
PubMed Central ID | PMC6801101 |
Grant List | R35 CA220499 / CA / NCI NIH HHS / United States R01 CA046595 / CA / NCI NIH HHS / United States K99 CA218686 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 GM008539 / GM / NIGMS NIH HHS / United States R01 CA240835 / CA / NCI NIH HHS / United States F31 CA220750 / CA / NCI NIH HHS / United States P01 CA094060 / CA / NCI NIH HHS / United States R03 CA212562 / CA / NCI NIH HHS / United States |