IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer
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Authors
Samanta, SanjoyGuru, Santosh
Elaimy, Ameer L.
Amante, John J.
Ou, Jianhong
Yu, Jun
Zhu, Lihua Julie
Mercurio, Arthur M.
UMass Chan Affiliations
UMass Metabolic NetworkGraduate School of Biomedical Sciences, MD/PhD Program
Department of Molecular, Cell and Cancer Biology
Document Type
Journal ArticlePublication Date
2018-05-29Keywords
RNA-binding proteinTAZ
Wnt
breast cancer
stem cells
Amino Acids, Peptides, and Proteins
Cancer Biology
Cell Biology
Cells
Neoplasms
Nucleic Acids, Nucleotides, and Nucleosides
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Show full item recordAbstract
Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with many aggressive cancers and implicated in the function of breast cancer stem cells (CSCs). The mechanisms involved, however, are poorly understood. We observed that IMP3 facilitates the activation of TAZ, a transcriptional co-activator of Hippo signaling that is necessary for the function of breast CSCs. The mechanism by which IMP3 activates TAZ involves both mRNA stability and transcriptional regulation. IMP3 stabilizes the mRNA of an alternative WNT ligand (WNT5B) indirectly by repressing miR145-5p, which targets WNT5B, resulting in TAZ activation by alternative WNT signaling. IMP3 also facilitates the transcription of SLUG, which is necessary for TAZ nuclear localization and activation, by a mechanism that is also mediated by WNT5B. These results demonstrate that TAZ can be regulated by an mRNA-binding protein and that this regulation involves the integration of Hippo and alternative WNT-signaling pathways.Source
Cell Rep. 2018 May 29;23(9):2559-2567. doi: 10.1016/j.celrep.2018.04.113. Link to article on publisher's site
DOI
10.1016/j.celrep.2018.04.113Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29359PubMed ID
29847788Related Resources
Rights
Copyright 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2018.04.113
Scopus Count
Except where otherwise noted, this item's license is described as Copyright 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).