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IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer

Sanjoy Samanta1, Santosh Guru1, Ameer L Elaimy1

  • 1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.

Cell Reports
|May 31, 2018
PubMed

Insights

Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) activates breast cancer stem cell functions by regulating TAZ. IMP3 stabilizes WNT5B mRNA and enhances SLUG transcription, integrating Hippo and WNT signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is an oncofetal protein linked to aggressive cancers.
  • IMP3 plays a role in breast cancer stem cell (CSC) function, but the underlying mechanisms are unclear.
  • TAZ, a transcriptional co-activator, is crucial for breast CSC function and is regulated by the Hippo signaling pathway.

Purpose of the Study:

  • To elucidate the mechanisms by which IMP3 influences breast cancer stem cell function.
  • To investigate the role of IMP3 in the activation of TAZ, a key regulator of breast CSCs.
  • To understand how IMP3 integrates Hippo and WNT signaling pathways in breast cancer.

Main Methods:

  • Investigated IMP3's effect on TAZ activation in breast CSCs.
  • Analyzed IMP3's role in mRNA stability and transcriptional regulation.
  • Examined the interaction between IMP3, miR145-5p, WNT5B, and SLUG.

Main Results:

  • IMP3 facilitates TAZ activation through both mRNA stability and transcriptional regulation.
  • IMP3 indirectly stabilizes WNT5B mRNA by repressing miR145-5p, leading to TAZ activation via alternative WNT signaling.
  • IMP3 promotes SLUG transcription, which is essential for TAZ nuclear localization and activation, also mediated by WNT5B.

Conclusions:

  • TAZ activation in breast CSCs can be regulated by the mRNA-binding protein IMP3.
  • IMP3 integrates Hippo and alternative WNT signaling pathways to control breast CSC function.
  • This study reveals a novel mechanism of TAZ regulation involving IMP3 and WNT5B in aggressive cancers.
Keywords:
RNA-binding proteinTAZWntbreast cancerstem cells

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