Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F16%3A00467979" target="_blank" >RIV/61388971:_____/16:00467979 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/16:10330146
Result on the web
<a href="http://dx.doi.org/10.1016/j.yexcr.2016.10.018" target="_blank" >http://dx.doi.org/10.1016/j.yexcr.2016.10.018</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.yexcr.2016.10.018" target="_blank" >10.1016/j.yexcr.2016.10.018</a>
Alternative languages
Result language
angličtina
Original language name
Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis
Original language description
he general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. nOur results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis. Surprisingly, YAP1 was found to positively regulate C-MYC mRNA levels in complex with TEAD1, while it negatively regulates C-MYC levels in cooperation with MST1. Hence, YAP1 serves as a rheostat for C-MYC, which is regulated by MST1. In addition, depletion of MST1 stimulates lactate production, whereas the specific depletion of TEAD1 has an opposite effect. The inhibition of lactate production and cellular proliferation induced by shikonin also depends on the Hippo pathway activity. Finally, a bioinformatic analysis revealed conserved TEAD-binding motifs in the C-MYC and GLUT1 promoters providing another molecular data supporting our observations. nIn summary, regulation of glucose metabolism could serve as a new tumor suppressor mechanism orchestrated by the Hippo signaling pathway.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EE - Microbiology, virology
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Experimental Cell Research
ISSN
0014-4827
e-ISSN
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Volume of the periodical
349
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
273-281
UT code for WoS article
000389163200008
EID of the result in the Scopus database
2-s2.0-84997096217