University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; Graduate School of Biomedical Sciences. MD/PhD Program; UMass Metabolic Network

Publication Date

2018-05-29

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Cell Biology | Cells | Neoplasms | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

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.

Keywords

RNA-binding protein, TAZ, Wnt, breast cancer, stem cells

Rights and Permissions

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/).

DOI of Published Version

10.1016/j.celrep.2018.04.113

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

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cell reports

PubMed ID

29847788

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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