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Cancer stem cells

TAZ takes centre stage

Nature Reviews Cancer volume 12, pages 82–83 (2012)Cite this article

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TAZ was required to sustain self-renewal of breast CSCs and to induce their tumorigenic potential.

Cordenonsi et al. found that a TAZ gene expression signature was over-represented in poorly differentiated breast tumours compared with well-differentiated low-grade tumours. The expression of TAZ-target genes correlated with stem cell signatures and an increased probability of metastasis. Consistent with these findings, TAZ was required to sustain self-renewal of breast CSCs and to induce their tumorigenic potential. TAZ was also shown to induce the property of self-renewal in non-CSCs. These authors also found that the levels of TAZ protein increase during EMT and that this is required for mammosphere formation, which is promoted by EMT. What is the link between EMT and TAZ activation? They found that the regulation of cell polarity is a key determinant. TAZ is phosphorylated by the Hippo pathway tyrosine kinases LATS1 and LATS2, and MST1 and MST2, leading to TAZ protein degradation. Cordenonsi et al. showed that the cell polarity regulator Scribble promotes the interaction between these Hippo pathway kinases and TAZ at the cell membrane. However, EMT results in the removal of Scribble from the cell membrane, thus releasing TAZ from this negative regulation. Therefore, EMT promotes the stabilization of TAZ, thereby enabling its translocation to the nucleus where it has been shown to regulate gene expression.

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References

ORIGINAL RESEARCH PAPERS

  1. Bhat, K. P. L. et al. The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant gioma. Genes Dev. 25, 2594–2609 (2011)Article

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  2. Cordenonsi, M. et al. The hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147, 759–772 (2011)Article

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FURTHER READING

  1. Martin-Belmonte, F. & Perez-Moreno, M. Epithelial cell polarity, stem cells and cancer. Nature Rev. Cancer 12, 23–38 (2012)

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Authors and Affiliations

  1. Consulting Editor, NCI–Nature Pathway Interaction Database,

    Mhairi Skinner

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  1. Mhairi Skinner
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Skinner, M. TAZ takes centre stage. Nat Rev Cancer 12, 82–83 (2012). https://doi.org/10.1038/nrc3210

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