mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by
activating the transcriptional coactivators YAP and TAZ.
Authors Edwards DN, Ngwa VM, Wang S, Shiuan E, Brantley-Sieders DM, Kim LC, Reynolds AB,
Chen J
Submitted By Submitted Externally on 3/23/2018
Status Published
Journal Science signaling
Year 2017
Date Published 12/1/2017
Volume : Pages 10 : Not Specified
PubMed Reference 29208682
Abstract Malignant tumors reprogram cellular metabolism to support cancer cell
proliferation and survival. Although most cancers depend on a high rate of
aerobic glycolysis, many cancer cells also display addiction to glutamine.
Glutamine transporters and glutaminase activity are critical for glutamine
metabolism in tumor cells. We found that the receptor tyrosine kinase EphA2
activated the TEAD family transcriptional coactivators YAP and TAZ (YAP/TAZ),
likely in a ligand-independent manner, to promote glutamine metabolism in cells
and mouse models of HER2-positive breast cancer. Overexpression of EphA2 induced
the nuclear accumulation of YAP and TAZ and increased the expression of YAP/TAZ
target genes. Inhibition of the GTPase Rho or the kinase ROCK abolished
EphA2-dependent YAP/TAZ nuclear localization. SilencingYAPorTAZsubstantially
reduced the amount of intracellular glutamate through decreased expression
ofSLC1A5andGLS, respectively, genes that encode proteins that promote glutamine
uptake and metabolism. The regulatory DNA elements of bothSLC1A5andGLScontain
TEAD binding sites and were bound by TEAD4 in an EphA2-dependent manner. In
patient breast cancer tissues,EphA2expression positively correlated with that
ofYAPandTAZ, as well as that ofGLSandSLC1A5Although high expression
ofEphA2predicted enhanced metastatic potential and poor patient survival, it
also rendered HER2-positive breast cancer cells more sensitive to glutaminase
inhibition. The findings define a previously unknown mechanism of EphA2-mediated
glutaminolysis through YAP/TAZ activation in HER2-positive breast cancer and
identify potential therapeutic targets in patients.




Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.