| Literature DB >> 25670079 |
Jia Xu1, Sunil Acharya2, Ozgur Sahin1, Qingling Zhang1, Yohei Saito1, Jun Yao1, Hai Wang1, Ping Li1, Lin Zhang2, Frank J Lowery2, Wen-Ling Kuo1, Yi Xiao1, Joe Ensor3, Aysegul A Sahin4, Xiang H-F Zhang5, Mien-Chie Hung6, Jitao David Zhang7, Dihua Yu8.
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.Entities:
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Year: 2015 PMID： 25670079 PMCID： PMC4325275 DOI： 10.1016/j.ccell.2014.11.025
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743