Department of Molecular, Cell and Cancer Biology; Graduate School of Biomedical Sciences. MD/PhD Program; UMass Metabolic Network
Amino Acids, Peptides, and Proteins | Cancer Biology | Cell Biology | Cells | Neoplasms | Nucleic Acids, Nucleotides, and Nucleosides
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.
RNA-binding protein, TAZ, Wnt, breast cancer, stem cells
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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
Cell Rep. 2018 May 29;23(9):2559-2567. doi: 10.1016/j.celrep.2018.04.113. Link to article on publisher's site
Samanta, Sanjoy; Guru, Santosh; Elaimy, Ameer L.; Amante, John J.; Ou, Jianhong; Yu, Jun; Zhu, Lihua Julie; and Mercurio, Arthur M., "IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer" (2018). University of Massachusetts Medical School Faculty Publications. 1587.
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