@article{bb4382167bc44357a14c2e0861a8006e,
title = "Cbx8 Acts Non-canonically with Wdr5 to Promote Mammary Tumorigenesis",
abstract = "Chromatin-mediated processes influence the development and progression of breast cancer. Using murine mammary carcinoma-derived tumorspheres as a functional readout for an aggressive breast cancer phenotype, we performed a loss-of-function screen targeting 60 epigenetic regulators. We identified the Polycomb protein Cbx8 as a key regulator of mammary carcinoma both in vitro and in vivo. Accordingly, Cbx8 is overexpressed in human breast cancer and correlates with poor survival. Our genomic analyses revealed that Cbx8 positively regulates Notch signaling by maintaining H3K4me3 levels on Notch-network gene promoters. Ectopic expression of Notch1 partially rescues tumorsphere formation in Cbx8-depleted cells. We find that Cbx8 associates with non-PRC1 complexes containing the H3K4 methyltransferase complex component WDR5, which together regulate Notch gene expression. Thus, our study implicates a key non-canonical role for Cbx8 in promoting breast tumorigenesis.",
author = "Chung, {Chi Yeh} and Zhen Sun and Gavriel Mullokandov and Almudena Bosch and Qadeer, {Zulekha A.} and Esma Cihan and Zachary Rapp and Ramon Parsons and Aguirre-Ghiso, {Julio A.} and Farias, {Eduardo F.} and Brown, {Brian D.} and Alexandre Gaspar-Maia and Emily Bernstein",
note = "Funding Information: The authors thank M. Mahajan, O. Jabado, and H. Shah from the ISMMS Genomics Core Facility, members of the E.B. lab, S. Aaronson lab, I. Aifantis lab, G. Peters lab, F. Hof lab, G. de Haan lab, D. Placantonakis lab, J. Wang lab, S. Frye lab, and I. Lemischka lab, M. Walsh, V. Gouon-Evans, J. Jin, W. Guo, N. Bansal, and M.S. Sosa for advice, reagents, and technical support. This work was supported by the Office of Research Infrastructure of the NIH (award number S10OD018522 ), the Department of Defense Breast Cancer Research Program award BC100975 , a New York Stem Cell Foundation-Druckenmiller fellowship to A.G.-M., NCI T32 T32CA078207-11 to Z.A.Q., a Helmsley Trust Award to G.M., an NIH Pathfinder Award ( DP2DK083052-01 ) and Juvenile Diabetes Research Foundation award ( JDRF-17-2010-770 ) to B.D.B., R01 CA82783 and R01CA184016 to R.P., a Samuel Waxman Cancer Research Foundation Tumor Dormancy Program award to J.A.A.-G., E.F.F., and E.B., and The JJR and Mary Kay Foundations award to E.B. Publisher Copyright: {\textcopyright} 2016 The Author(s)",
year = "2016",
month = jul,
day = "12",
doi = "10.1016/j.celrep.2016.06.002",
language = "English",
volume = "16",
pages = "472--486",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}