Publication: Self-reinforcing loop of amphiregulin and Y-box binding protein-1 contributes to poor outcomes in ovarian cancer
Issued Date
2014-05-29
Resource Type
ISSN
14765594
09509232
09509232
Other identifier(s)
2-s2.0-84901818936
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Oncogene. Vol.33, No.22 (2014), 2846-2856
Suggested Citation
N. Panupinthu, S. Yu, D. Zhang, F. Zhang, M. Gagea, Y. Lu, J. R. Grandis, S. E. Dunn, H. Y. Lee, G. B. Mills Self-reinforcing loop of amphiregulin and Y-box binding protein-1 contributes to poor outcomes in ovarian cancer. Oncogene. Vol.33, No.22 (2014), 2846-2856. doi:10.1038/onc.2013.259 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/33260
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Self-reinforcing loop of amphiregulin and Y-box binding protein-1 contributes to poor outcomes in ovarian cancer
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.