IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer

Cell Reports
Sanjoy SamantaArthur M Mercurio

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.

Citations

Aug 30, 2019·Cell Communication and Signaling : CCS·Shaojie JiangXiaoming Yang
Jun 20, 2019·Cells·Hyunbin D HuhHyun Woo Park
Feb 6, 2020·Frontiers in Cell and Developmental Biology·Caterina Mancarella, Katia Scotlandi
Mar 20, 2021·Seminars in Cancer Biology·Rui ZhangSuling Liu
May 22, 2021·Frontiers in Cell and Developmental Biology·Sarocha SuthonSusan A Krum
May 27, 2021·Scientific Reports·Daniela Bevanda GliboSnježana Tomić
Jun 12, 2021·Cancer Cell International·Jing ChenAlexander Tobias Teichmann

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Methods Mentioned

BETA
immunoprecipitation
GTPase
transfection

Software Mentioned

cBioPortal
GSEA

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