Widespread FRA1-Dependent Control of Mesenchymal Transdifferentiation Programs in Colorectal Cancer Cells

Diesch, Jeannine, Sanij, Elaine, Gilan, Omer, Love, Christopher, Tran, Hoanh, Fleming, Nicholas I., Ellul, Jason, Amalia, Marcia, Haviv, Izhak, Pearson, Richard B., Tulchinsky, Eugene, Mariadason, John M., Sieber, Oliver M., Hannan, Ross D. and Dhillon, Amardeep S. (2014) Widespread FRA1-Dependent Control of Mesenchymal Transdifferentiation Programs in Colorectal Cancer Cells. PLoS One, 9 3: e88950.1-e88950.11. doi:10.1371/journal.pone.0088950

Author Diesch, Jeannine
Sanij, Elaine
Gilan, Omer
Love, Christopher
Tran, Hoanh
Fleming, Nicholas I.
Ellul, Jason
Amalia, Marcia
Haviv, Izhak
Pearson, Richard B.
Tulchinsky, Eugene
Mariadason, John M.
Sieber, Oliver M.
Hannan, Ross D.
Dhillon, Amardeep S.
Title Widespread FRA1-Dependent Control of Mesenchymal Transdifferentiation Programs in Colorectal Cancer Cells
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-03-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0088950
Open Access Status DOI
Volume 9
Issue 3
Start page e88950.1
End page e88950.11
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
1100 Agricultural and Biological Sciences
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.
Keyword Colon-Carcinoma Cells
Fos Family-Members
Differential Expression
Transcription Factors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
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