ECM1 promotes the Warburg effect through EGF-mediated activation of PKM2

Title
ECM1 promotes the Warburg effect through EGF-mediated activation of PKM2
Author
신인철
Keywords
ECM1; PKM2; Warburg effect; GLUT1; LDHA
Issue Date
2015-02
Publisher
ELSEVIER SCIENCE INC
Citation
CELLULAR SIGNALLING, v. 27, NO 2, Page. 228-235
Abstract
The Warburg effect is an oncogenic metabolic switch that allows cancer cells to take up more glucose than normal cells and favors anaerobic glycolysis. Extracellular matrix protein 1 (ECM1) is a secreted glycoprotein that is overexpressed in various types of carcinoma. Using two-dimensional digest-liquid chromatography-mass spectrometry (LC-MS)/MS, we showed that the expression of proteins associated with the Warburg effect was upregulated in trastuzumab-resistant BT-474 cells that overexpressed ECM1 compared to control cells. We further demonstrated that ECM1 induced the expression of genes that promote the Warburg effect, such as glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and hypoxia-inducible factor 1 alpha (HIF-1 alpha). The phosphorylation status of pyruvate kinase M2 (PKM-2) at Ser37, which is responsible for the expression of genes that promote the Warburg effect, was affected by the modulation of ECM1 expression. Moreover, EGF-dependent ERK activation that was regulated by ECM1 induced not only PKM2 phosphorylation but also gene expression of GLUT1 and LDHA. These findings provide evidence that ECM1 plays an important role in promoting the Warburg effect mediated by PKM2. (C) 2014 Elsevier Inc All rights reserved.
URI
http://www.sciencedirect.com/science/article/pii/S0898656814003507http://hdl.handle.net/20.500.11754/22419
ISSN
0898-6568; 1873-3913
DOI
10.1016/j.cellsig.2014.11.004
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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