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Hedgehog-EGFR cooperation response genes determine the onogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells
VerfasserEberl, Markus ; Klingler, Stefan ; Mangelberger, Doris ; Loipetzberger, Andrea ; Damhofer, Helene ; Zoidl, Kerstin ; Schnidar, Harald ; Hache, Hendrik ; Bauer, Hans-Christian In der Gemeinsamen Normdatei der DNB nachschlagen ; Solca, Flavio ; Hauser-Kronberger, Cornelia In der Gemeinsamen Normdatei der DNB nachschlagen ; Ermilov, Alexandre N. ; Verhaegen, Monique E. ; Bichakjian, Christopher K. ; Dlugosz, Andrzej A. ; Nietfeld, Wilfried ; Sibilia, Maria In der Gemeinsamen Normdatei der DNB nachschlagen ; Lehrach, Hans ; Wierling, Christoph In der Gemeinsamen Normdatei der DNB nachschlagen ; Aberger, Fritz In der Gemeinsamen Normdatei der DNB nachschlagen
Erschienen in
EMBO Molecular Medicine, Heidelberg, 2012, Jg. Mar, H. 4, S. 218-233
ErschienenEMBO Press, 2012
SpracheEnglisch
DokumenttypAufsatz in einer Zeitschrift
Schlagwörter (EN)cancer / epidermal growth / factor receptor / Hedgehog signallling / Signal transduction
ISSN1757-4684
URNurn:nbn:at:at-ubs:3-357 Persistent Identifier (URN)
DOI10.1002/emmm.201100201 
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Hedgehog-EGFR cooperation response genes determine the onogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells [1.67 mb]
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Zusammenfassung (Englisch)

Inhibition of Hedgehog (HH)/GLI signalling in cancer is a promising therapeutic approach. Interactions between HH/GLI and other oncogenic pathways affect the strength and tumourigenicity of HH/GLI. Cooperation of HH/GLI with epidermal growth factor receptor (EGFR) signalling promotes transformation and cancer cell proliferation in vitro. However, the in vivo relevance of HH-EGFR signal integration and the critical downstream mediators are largely undefined. In this report we show that genetic and pharmacologic inhibition of EGFR signalling reduces tumour growth in mouse models of HH/GLI driven basal cell carcinoma (BCC). We describe HH-EGFR cooperation response genes including SOX2, SOX9, JUN, CXCR4 and FGF19 that are synergistically activated by HH-EGFR signal integration and required for in vivo growth of BCC cells and tumour-initiating pancreatic cancer cells. The data validate EGFR signalling as drug target in HH/GLI driven cancers and shed light on the molecular processes controlled by HH-EGFR signal cooperation, providing new therapeutic strategies based on combined targeting of HH-EGFR signalling and selected downstream target genes.