YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29
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Organ development is a complex process governed by the interplay of several signalling pathways that have critical functions in the regulation of cell growth and proliferation. Over the past years, the Hippo pathway has emerged as a key regulator of organ size. Perturbation of this pathway has been shown to play important roles in tumorigenesis. YAP, the main downstream target of the mammalian Hippo pathway, promotes organ growth, yet the underlying molecular mechanism of this regulation remains unclear. Here we provide evidence that YAP activates the mammalian target of rapamycin (mTOR), a major regulator of cell growth. We have identified the tumour suppressor PTEN, an upstream negative regulator of mTOR, as a critical mediator of YAP in mTOR regulation. We demonstrate that YAP downregulates PTEN by inducing miR-29 to inhibit PTEN translation. Last, we show that PI(3)K–mTOR is a pathway modulated by YAP to regulate cell size, tissue growth and hyperplasia. Our studies reveal a functional link between Hippo and PI(3)K–mTOR, providing a molecular basis for the coordination of these two pathways in organ size regulation.
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Yap de-represses mTOR by inhibiting the expression of the phosphatase Pten via the Pten-targeting miRNA miR-29.
“Additionally, the Hippo effector Yap de-represses mTOR by inhibiting the expression of the phosphatase Pten via the Pten-targeting miRNA miR-29 (133).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [133]
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- Authors
- Tumaneng, K., Schlegelmilch, K., Russell, R. C., Yimlamai, D., Basnet, H., Mahadevan, N., Fitamant, J., Bardeesy, N., Camargo, F. D., & Guan, K.-L.
- Affiliations
- University of California San Diego (US)
- Harvard University (US)
- Corresponding author
- Guan, Kun-Liang
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2012-11-11
- Volume
- 14
- Issue
- 12
- Pages
- 1322-1329
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4019071
- OpenAlex
- W1992845452
- Cited by
- 453
- References
- 33
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 29 · 2023: 20 · 2022: 30 · 2021: 42 · 2020: 39 · 2019: 50 · 2018: 44 · 2017: 45 · 2016: 27 · 2015: 41 · 2014: 32 · 2013: 18 · 2012: 2
- FWCI
- 14.08
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA136567)
- National Institute of General Medical Sciences (T32GM007752)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK105351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- YAP, Hippo signaling pathway, PTEN, miR-29, pathway crosstalk, organ size control, cell growth, cell proliferation, hyperplasia, tumour suppressor
- MeSH terms
- Serine-Threonine Kinase 3, YAP-Signaling Proteins, Hippo Kinases, Animals, Cell Line, Chromones, Flow Cytometry, Humans, Liver, Male, Mice, Transgenic, Morpholines, Phosphoproteins, Proto-Oncogene Proteins, Hepatocyte Growth Factor, Protein Serine-Threonine Kinases, Mice, Knockout, Cell Cycle Proteins, MicroRNAs, Chromatin Immunoprecipitation, Adaptor Proteins, Signal Transducing, PTEN Phosphohydrolase, Mice, High-Throughput Nucleotide Sequencing, Real-Time Polymerase Chain Reaction
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