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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/33260
Title: Self-reinforcing loop of amphiregulin and Y-box binding protein-1 contributes to poor outcomes in ovarian cancer
Authors: N. Panupinthu
S. Yu
D. Zhang
F. Zhang
M. Gagea
Y. Lu
J. R. Grandis
S. E. Dunn
H. Y. Lee
G. B. Mills
University of Texas MD Anderson Cancer Center
Mahidol University
University of Pittsburgh
The University of British Columbia
Konyang University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 29-May-2014
Citation: Oncogene. Vol.33, No.22 (2014), 2846-2856
Abstract: The Y-box binding protein-1 (YB-1) transcription factor is associated with unfavorable clinical outcomes. However, the mechanisms underlying this association remain to be fully elucidated. We demonstrate that YB-1 phosphorylation, indicative of YB-1 activation, is a powerful marker of outcomes for ovarian cancer patients. In ovarian cancer, YB-1 phosphorylation is induced by activation of the lysophosphatidic acid (LPA) receptor (LPAR) via SRC-dependent transactivation of the epidermal growth factor receptor (EGFR) that is coupled to MAPK/p90 ribosomal S6 kinase (p90RSK), but not phosphatidylinositol 3-kinase (PI3K)/AKT signaling. Activation of the LPAR/SRC/EGFR/MAPK/p90RSK/YB-1 axis leads to production of the EGFR ligand amphiregulin (AREG). AREG induces ongoing YB-1 phosphorylation as well as YB-1-dependent AREG expression, thus constituting an AREG/YB-1 self-reinforcing loop. Disruption of transactivation of the EGFR and the downstream self-reinforcing loop decreases invasiveness of ovarian cancer cells in vitro and limits ovarian cancer growth in xenograft models. These findings established the regulation and significance of YB-1 phosphorylation, therefore further exploration of this signaling axis as a therapeutic avenue in ovarian cancer is warranted. © 2014 Macmillan Publishers Limited All rights reserved.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84901818936&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/33260
ISSN: 14765594
09509232
Appears in Collections:Scopus 2011-2015

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