Journal
EMBO MOLECULAR MEDICINE
Volume 4, Issue 3, Pages 218-233Publisher
WILEY
DOI: 10.1002/emmm.201100201
Keywords
cancer; epidermal growth factor receptor; Hedgehog signalling; signal transduction
Categories
Funding
- Austrian Science Fund FWF [P20652]
- Austrian genome program Gen-AU
- German Ministry for Research (BMBF) [MoGLI 0315394A]
- Max Planck Society
- NGFN-Plus [01GS08105]
- University of Salzburg
- Doctoral Program Inflammation and Immunity [DK W1212]
- EC [LSHC-CT-2006-037731]
- Austrian Federal Government's GEN-AU [GZ 200.147/1-VI/1a/2006, 820966]
- NIH [CA087837, CA118875]
- Austrian Science Fund (FWF) [W1213, P20652] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available