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Microenvironment

Tumour-promoting tissue mechanics

Nature Reviews Cancer volume 14, pages 296–297 (2014)Cite this article

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Tissue mechanics have been implicated in tumour progression but the underlying molecular mechanisms have been unclear. Now, Mouw et al. show that increased extracellular matrix (ECM) stiffness induces expression of the microRNA miR-18a in breast tissue, and this miRNA in turn targets the tumour suppressor PTEN.

The authors then identified and confirmed that miR-18a binds to and inhibits both the tumour suppressor PTEN and homeobox A9 (HOXA9). Furthermore, reduced levels of PTEN and HOXA9 proteins were correlated with greater tissue stiffness, and either inhibiting stiffening or knocking down miR-18a in cells grown on a stiff gel rescued the expression of both proteins. In addition, the level of phosphorylated AKT was increased when PTEN expression was lost, which indicates that the PI3K arm of PTEN signalling was affected.

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References

  1. Mouw, J. K. et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nature Med. http://dx.doi.org/10.1038/nm.3497 (2014)

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  1. Isabel Lokody
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Lokody, I. Tumour-promoting tissue mechanics. Nat Rev Cancer 14, 296–297 (2014). https://doi.org/10.1038/nrc3727

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