Cited by 550Hippo pathway signaling and YAP/TAZMetabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancer

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AMPK modulates Hippo pathway activity to regulate energy homeostasis

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Wang, Wenqi, Xiao, Zhen-Dong, Li, Xu, Aziz, Kathryn E., Gan, Boyi, Johnson, Randy L., Chen, Junjie·2015·Nature Cell Biology

DOI 10.1038/ncb3113PMC PMC4380807

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Abstract

The Hippo pathway was discovered as a conserved tumour suppressor pathway restricting cell proliferation and apoptosis. However, the upstream signals that regulate the Hippo pathway in the context of organ size control and cancer prevention are largely unknown. Here, we report that glucose, the ubiquitous energy source used for ATP generation, regulates the Hippo pathway downstream effector YAP. We show that both the Hippo pathway and AMP-activated protein kinase (AMPK) were activated during glucose starvation, resulting in phosphorylation of YAP and contributing to its inactivation. We also identified glucose-transporter 3 (GLUT3) as a YAP-regulated gene involved in glucose metabolism. Together, these results demonstrate that glucose-mediated energy homeostasis is an upstream event involved in regulation of the Hippo pathway and, potentially, an oncogenic function of YAP in promoting glycolysis, thereby providing an exciting link between glucose metabolism and the Hippo pathway in tissue maintenance and cancer prevention.

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Authors: Wang, W., Xiao, Z.-D., Li, X., Aziz, K. E., Gan, B., Johnson, R. L., & Chen, J.
Affiliations: The University of Texas System (US)
The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Chen, Junjie
ORCID: Wang, Wenqi
Xiao, Zhen-Dong
Li, Xu
Aziz, Kathryn E.
Gan, Boyi
Johnson, Randy L.
Chen, Junjie
Venue: Nature Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2015-03-09
Volume: 17
Issue: 4
Pages: 490-499
ISSN: 1465-7392 (ISSN-L)
1476-4679
DOI: 10.1038/ncb3113
PMC: PMC4380807
OpenAlex: W2020511240
Cited by: 549
References: 40
Citations by year: 2026: 31 · 2025: 51 · 2024: 57 · 2023: 40 · 2022: 53 · 2021: 55 · 2020: 72 · 2019: 43 · 2018: 52 · 2017: 41 · 2016: 33 · 2015: 19
FWCI: 25.72
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Cell Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Cancer Institute (CA 016672, R01CA089239, R01CA092312, R01CA181196, P30CA016672)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102611)
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 › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: AMPK, Hippo signaling pathway, YAP, energy homeostasis, glucose metabolism, glucose deprivation, GLUT3, YAP phosphorylation, organ size control, tumor suppression, glycolysis, cancer prevention
MeSH terms: Hippo Signaling Pathway, YAP-Signaling Proteins, Animals, Colonic Neoplasms, Energy Metabolism, Enzyme Activation, Female, Glucose, Glycolysis, HeLa Cells, Humans, Liver Neoplasms, Mice, Inbred C57BL, Phosphoproteins, Phosphorylation, Starvation, Transcription, Genetic, Protein Serine-Threonine Kinases, Cell Cycle Proteins, rho GTP-Binding Proteins, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Glucose Transporter Type 3, Mice, AMP-Activated Protein Kinases, HEK293 Cells

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AMPK modulates Hippo pathway activity to regulate energy homeostasis

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