Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32725
Title: Widespread FRA1-dependent control of mesenchymal transdifferentiation programs in colorectal cancer cells.
Authors: Diesch, J.
Sanij, E.
Gilan, O.
Love, C.
Tran, H.
Fleming, N. I.
Ellul, J.
Amalia, M.
Haviv, I.
Pearson, R. B.
Tulchinsky, Eugene
Mariadason, J. M.
Sieber, O. M.
Hannan, R. D.
Dhillon, A. S.
First Published: 21-Mar-2014
Publisher: Public Library of Science
Citation: PLoS One, 2014, 9 (3), pp. e88950-?
Abstract: Tumor invasion and metastasis involves complex remodeling of gene expression programs governing epithelial homeostasis. Mutational activation of the RAS-ERK is a frequent occurrence in many cancers and has been shown to drive overexpression of the AP-1 family transcription factor FRA1, a potent regulator of migration and invasion in a variety of tumor cell types. However, the nature of FRA1 transcriptional targets and the molecular pathways through which they promote tumor progression remain poorly understood. We found that FRA1 was strongly expressed in tumor cells at the invasive front of human colorectal cancers (CRCs), and that its depletion suppressed mesenchymal-like features in CRC cells in vitro. Genome-wide analysis of FRA1 chromatin occupancy and transcriptional regulation identified epithelial-mesenchymal transition (EMT)-related genes as a major class of direct FRA1 targets in CRC cells. Expression of the pro-mesenchymal subset of these genes predicted adverse outcomes in CRC patients, and involved FRA-1-dependent regulation and cooperation with TGFβ signaling pathway. Our findings reveal an unexpectedly widespread and direct role for FRA1 in control of epithelial-mesenchymal plasticity in CRC cells, and suggest that FRA1 plays an important role in mediating cross talk between oncogenic RAS-ERK and TGFβ signaling networks during tumor progression.
DOI Link: 10.1371/journal.pone.0088950
eISSN: 1932-6203
Links: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088950
http://hdl.handle.net/2381/32725
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014 Diesch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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