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YAP, PTEN and miR-29 size each other up

Nature Reviews Cancer volume 13, pages 4–5 (2013)Cite this article

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Crosstalk between the Hippo and TOR pathways has been indicated in studies of Drosophila melanogaster. Building on these findings, the authors showed that small interfering RNA (siRNA) knockdown of the LATS kinases, which inhibit YAP by phosphorylation, reduced YAP phosphorylation and activated mTOR complex 1 (mTORC1) and mTORC2 in MCF10A cells in vitro. In addition, overexpression or under-expression of YAP in cell lines in culture also affected the activity of mTORC1 and mTORC2, as did the overexpression of YAP in mouse intestine in vivo. Further in vitro and in vivo experiments showed that YAP activity affected the expression of PTEN, a known regulator of the PI3K pathway.

How does YAP regulate PTEN? Although YAP can regulate transcription with its DNA binding partner TEAD, it has no effect on PTEN transcription. YAP also has no effect on PTEN protein stability or modification. However, PTEN is targeted by a number of microRNAs, and the D. melanogaster homologue of YAP, Yorkie, regulates microRNA expression. The authors found that in cells overexpressing or under-expressing YAP, the miR-29 family is overexpressed or under-expressed, respectively. Recent studies have shown that PTEN is regulated by both miR-29a and miR-29b, and the authors showed that YAP–TEAD binds to the promoter of mir-29c and promotes its transcription. The promoters of mir-29a and mir-29b also contain TEAD consensus-binding sites, indicating that YAP seems to regulate PTEN through the direct regulation of miR-29 family members. Interestingly, although overexpression of miR-29 resulted in mTOR activation, it did not have a substantial effect on cell size.

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References

ORIGINAL RESEARCH PAPER

  1. Tumaneng, K. et al. YAP mediates crosstalk between the Hippo and PI3K-TOR pathways by suppressing PTEN via miR-29. Nature Cell Biol. 11 Nov 2012 (doi:10.1038/ncb2615)

FURTHER READING

  1. Chen, D. et al. LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nature Med. 18, 1511–1517 (2012)

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  1. Nicola McCarthy
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McCarthy, N. YAP, PTEN and miR-29 size each other up. Nat Rev Cancer 13, 4–5 (2013). https://doi.org/10.1038/nrc3422

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