SOX9 regulates ERBB signalling in pancreatic cancer development

Grimont, Adrien, Pinho, Andreia V., Cowley, Mark J., Augereau, Cécile, Mawson, Amanda, Giry-Laterriere, Marc, Van den Steen, Géraldine, Waddell, Nicola, Pajic, Marina, Sempoux, Christine, Wu, Jianmin, Grimmond, Sean M., Biankin, Andrew V., Lemaigre, Frédéric P., Rooman, Ilse and Jacquemin, Patrick (2014) SOX9 regulates ERBB signalling in pancreatic cancer development. Gut, 43 8: 1361.1-1361.10. doi:10.1136/gutjnl-2014-307075

Author Grimont, Adrien
Pinho, Andreia V.
Cowley, Mark J.
Augereau, Cécile
Mawson, Amanda
Giry-Laterriere, Marc
Van den Steen, Géraldine
Waddell, Nicola
Pajic, Marina
Sempoux, Christine
Wu, Jianmin
Grimmond, Sean M.
Biankin, Andrew V.
Lemaigre, Frédéric P.
Rooman, Ilse
Jacquemin, Patrick
Title SOX9 regulates ERBB signalling in pancreatic cancer development
Journal name Gut   Check publisher's open access policy
ISSN 0017-5749
Publication date 2014-10-21
Sub-type Article (original research)
DOI 10.1136/gutjnl-2014-307075
Open Access Status
Volume 43
Issue 8
Start page 1361.1
End page 1361.10
Total pages 10
Place of publication London, United Kingdom
Publisher B M J Group
Collection year 2015
Language eng
Formatted abstract
Objective: The transcription factor SOX9 was recently shown to stimulate ductal gene expression in pancreatic acinar-to-ductal metaplasia and to accelerate development of premalignant lesions preceding pancreatic ductal adenocarcinoma (PDAC). Here, we investigate how SOX9 operates in pancreatic tumourigenesis.

Design: We analysed genomic and transcriptomic data from surgically resected PDAC and extended the expression analysis to xenografts from PDAC samples and to PDAC cell lines. SOX9 expression was manipulated in human cell lines and mouse models developing PDAC.

Results: We found genetic aberrations in the SOX9 gene in about 15% of patient tumours. Most PDAC samples strongly express SOX9 protein, and SOX9 levels are higher in classical PDAC. This tumour subtype is associated with better patient outcome, and cell lines of this subtype respond to therapy targeting epidermal growth factor receptor (EGFR/ERBB1) signalling, a pathway essential for pancreatic tumourigenesis. In human PDAC, high expression of SOX9 correlates with expression of genes belonging to the ERBB pathway. In particular, ERBB2 expression in PDAC cell lines is stimulated by SOX9. Inactivating Sox9 expression in mice confirmed its role in PDAC initiation; it demonstrated that Sox9 stimulates expression of several members of the ERBB pathway and is required for ERBB signalling activity.

Conclusions: By integrating data from patient samples and mouse models, we found that SOX9 regulates the ERBB pathway throughout pancreatic tumourigenesis. Our work opens perspectives for therapy targeting tumourigenic mechanisms.
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
Institute for Molecular Bioscience - Publications
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Created: Thu, 27 Nov 2014, 13:48:59 EST by Katrina Garner-Moore on behalf of Institute for Molecular Bioscience