PMID- 25751139
OWN - NLM
STAT- MEDLINE
DCOM- 20150615
LR  - 20230708
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 17
IP  - 4
DP  - 2015 Apr
TI  - AMPK modulates Hippo pathway activity to regulate energy homeostasis.
PG  - 490-9
LID - 10.1038/ncb3113 [doi]
AB  - 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.
FAU - Wang, Wenqi
AU  - Wang W
AD  - Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard Houston, 
      Texas 77030, USA.
FAU - Xiao, Zhen-Dong
AU  - Xiao ZD
AD  - Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard Houston, 
      Texas 77030, USA.
FAU - Li, Xu
AU  - Li X
AD  - Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard Houston, 
      Texas 77030, USA.
FAU - Aziz, Kathryn E
AU  - Aziz KE
AD  - Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard Houston, 
      Texas 77030, USA.
FAU - Gan, Boyi
AU  - Gan B
AD  - 1] Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard 
      Houston, Texas 77030, USA [2] Cancer Biology Program, The University of Texas 
      Graduate School of Biomedical Science, 1515 Holcombe Boulevard Houston, Texas 
      77030, USA.
FAU - Johnson, Randy L
AU  - Johnson RL
AD  - 1] Cancer Biology Program, The University of Texas Graduate School of Biomedical 
      Science, 1515 Holcombe Boulevard Houston, Texas 77030, USA [2] Department of 
      Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard Houston, Texas 77030, USA.
FAU - Chen, Junjie
AU  - Chen J
AD  - 1] Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard 
      Houston, Texas 77030, USA [2] Cancer Biology Program, The University of Texas 
      Graduate School of Biomedical Science, 1515 Holcombe Boulevard Houston, Texas 
      77030, USA.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R01 CA092312/CA/NCI NIH HHS/United States
GR  - CA016672/CA/NCI NIH HHS/United States
GR  - R01 CA089239/CA/NCI NIH HHS/United States
GR  - R01 DK102611/DK/NIDDK NIH HHS/United States
GR  - R01 CA181196/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150309
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Glucose Transporter Type 3)
RN  - 0 (Phosphoproteins)
RN  - 0 (Slc2a3 protein, mouse)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yap1 protein, mouse)
RN  - EC 2.7.1.- (Lats1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Cell Cycle. 2015;14(13):1995-6. PMID: 25942485
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Animals
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/metabolism
MH  - Energy Metabolism
MH  - Enzyme Activation
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 3/biosynthesis/genetics/*metabolism
MH  - Glycolysis
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - Liver Neoplasms/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Starvation
MH  - Transcription, Genetic
MH  - YAP-Signaling Proteins
MH  - rho GTP-Binding Proteins/metabolism
PMC - PMC4380807
MID - NIHMS656543
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests.
EDAT- 2015/03/10 06:00
MHDA- 2015/06/16 06:00
PMCR- 2015/10/01
CRDT- 2015/03/10 06:00
PHST- 2014/06/18 00:00 [received]
PHST- 2015/01/15 00:00 [accepted]
PHST- 2015/03/10 06:00 [entrez]
PHST- 2015/03/10 06:00 [pubmed]
PHST- 2015/06/16 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - ncb3113 [pii]
AID - 10.1038/ncb3113 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2015 Apr;17(4):490-9. doi: 10.1038/ncb3113. Epub 2015 Mar 9.