@article{443707f420c94ad0a39cbeb576b72f3b,
title = "14-3-3ζ Turns TGF-β's Function from Tumor Suppressor to Metastasis Promoter in Breast Cancer by Contextual Changes of Smad Partners from p53 to Gli2",
abstract = "Transforming growth factor β (TGF-β) functions as a tumor suppressor in premalignant cells but as a metastasis promoter in cancer cells. The dichotomous functions of TGF-β are proposed to be dictated by different partners of its downstream effector Smads. However, the mechanism for the contextual changes of Smad partners remained undefined. Here, we demonstrate that 14-3-3ζ destabilizes p53, a Smad partner in premalignant mammary epithelial cells, by downregulating 14-3-3σ, thus turning off TGF-β's tumor suppression function. Conversely, 14-3-3ζ stabilizes Gli2 in breast cancer cells, and Gli2 partners with Smads to activate PTHrP and promote TGF-β-induced bone metastasis. The 14-3-3ζ-driven contextual changes of Smad partners from p53 to Gli2 may serve as biomarkers and therapeutic targets of TGF-β-mediated cancer progression.",
author = "Jia Xu and Sunil Acharya and Ozgur Sahin and Qingling Zhang and Yohei Saito and Jun Yao and Hai Wang and Ping Li and Lin Zhang and Lowery, {Frank J.} and Kuo, {Wen Ling} and Yi Xiao and {Ensor, Jr.}, {Joe Edward} and Sahin, {Aysegul A.} and Zhang, {Xiang H F} and Hung, {Mien Chie} and Zhang, {Jitao David} and Dihua Yu",
note = "Funding Information: This work was supported by NIH grants P30-CA 16672 (MDACC), PO1-CA099031 project 4 (D.Y.), and RO1-CA112567-07 (D.Y.); Susan G. Komen Foundation grant KG091020 (D.Y.); Cancer Prevention Research Institute of Texas grant RP100726 (D.Y.); METAvivor research grant (D.Y.); DOD Pre-doctoral Fellowship W81XWH-10-1-0238 (J.X.); and a Sowell-Huggins Professorship (D.Y.) and Pre-doctoral Fellowship in Cancer Research (L.Z.). D.Y. is the Hubert L. & Olive Stringer Distinguished Chair in Basic Science at MD Anderson Cancer Center. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = feb,
day = "9",
doi = "10.1016/j.ccell.2014.11.025",
language = "English (US)",
volume = "27",
pages = "177--192",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}