RGD Reference Report - Frequent deregulations in the hedgehog signaling network and cross-talks with the epidermal growth factor receptor pathway involved in cancer progression and targeted therapies. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Frequent deregulations in the hedgehog signaling network and cross-talks with the epidermal growth factor receptor pathway involved in cancer progression and targeted therapies.

Authors: Mimeault, M  Batra, SK 
Citation: Mimeault M and Batra SK, Pharmacol Rev. 2010 Sep;62(3):497-524.
RGD ID: 5510013
Pubmed: PMID:20716670   (View Abstract at PubMed)
PMCID: PMC2964899   (View Article at PubMed Central)
DOI: DOI:10.1124/pr.109.002329   (Journal Full-text)

The hedgehog (Hh)/glioma-associated oncogene (GLI) signaling network is among the most important and fascinating signal transduction systems that provide critical functions in the regulation of many developmental and physiological processes. The coordinated spatiotemporal interplay of the Hh ligands and other growth factors is necessary for the stringent control of the behavior of diverse types of tissue-resident stem/progenitor cells and their progenies. The activation of the Hh cascade might promote the tissue regeneration and repair after severe injury in numerous organs, insulin production in pancreatic beta-cells, and neovascularization. Consequently, the stimulation of the Hh pathway constitutes a potential therapeutic strategy to treat diverse human disorders, including severe tissue injuries; diabetes mellitus; and brain, skin, and cardiovascular disorders. In counterbalance, a deregulation of the Hh signaling network might lead to major tissular disorders and the development of a wide variety of aggressive and metastatic cancers. The target gene products induced through the persistent Hh activation can contribute to the self-renewal, survival, migration, and metastasis of cancer stem/progenitor cells and their progenies. Moreover, the pivotal role mediated through the Hh/GLI cascade during cancer progression also implicates the cooperation with other oncogenic products, such as mutated K-RAS and complex cross-talk with different growth factor pathways, including tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR), Wnt/beta-catenin, and transforming growth factor-beta (TGF-beta)/TGF-beta receptors. Therefore, the molecular targeting of distinct deregulated gene products, including Hh and EGFR signaling components and other signaling elements that are frequently deregulated in highly tumorigenic cancer-initiating cells and their progenies, might constitute a potential therapeutic strategy to eradicate the total cancer cell mass. Of clinical interest is that these multitargeted approaches offer great promise as adjuvant treatments for improving the current antihormonal therapies, radiotherapies, and/or chemotherapies against locally advanced and metastatic cancers, thereby preventing disease relapse and the death of patients with cancer.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DHHHumanHedgehog signaling pathway   TAS  RGD 
DhhRatHedgehog signaling pathway   ISODHH (Homo sapiens) RGD 
DhhMouseHedgehog signaling pathway   ISODHH (Homo sapiens) RGD 
GLI1HumanHedgehog signaling pathway   TAS  RGD 
GLI2HumanHedgehog signaling pathway   TAS  RGD 
GLI3HumanHedgehog signaling pathway   TAS  RGD 
Gli1RatHedgehog signaling pathway   ISOGLI1 (Homo sapiens) RGD 
Gli1MouseHedgehog signaling pathway   ISOGLI1 (Homo sapiens) RGD 
Gli2RatHedgehog signaling pathway   ISOGLI2 (Homo sapiens) RGD 
Gli2MouseHedgehog signaling pathway   ISOGLI2 (Homo sapiens) RGD 
Gli3RatHedgehog signaling pathway   ISOGLI3 (Homo sapiens) RGD 
Gli3MouseHedgehog signaling pathway   ISOGLI3 (Homo sapiens) RGD 
HHATHumanHedgehog signaling pathway   TAS  RGD 
HhatMouseHedgehog signaling pathway   ISOHHAT (Homo sapiens) RGD 
IHHHumanHedgehog signaling pathway   TAS  RGD 
IhhRatHedgehog signaling pathway   ISOIHH (Homo sapiens) RGD 
IhhMouseHedgehog signaling pathway   ISOIHH (Homo sapiens) RGD 
PTCH1HumanHedgehog signaling pathway   TAS  RGD 
PTCH2HumanHedgehog signaling pathway   TAS  RGD 
Ptch1RatHedgehog signaling pathway   ISOPTCH1 (Homo sapiens) RGD 
Ptch1MouseHedgehog signaling pathway   ISOPTCH1 (Homo sapiens) RGD 
Ptch2MouseHedgehog signaling pathway   ISOPTCH2 (Homo sapiens) RGD 
SHHHumanHedgehog signaling pathway   TAS  RGD 
SMOHumanHedgehog signaling pathway   TAS  RGD 
SUFUHumanHedgehog signaling pathway   TAS  RGD 
ShhRatHedgehog signaling pathway   ISOSHH (Homo sapiens) RGD 
ShhMouseHedgehog signaling pathway   ISOSHH (Homo sapiens) RGD 
SmoRatHedgehog signaling pathway   ISOSMO (Homo sapiens) RGD 
SmoMouseHedgehog signaling pathway   ISOSMO (Homo sapiens) RGD 
SufuMouseHedgehog signaling pathway   ISOSUFU (Homo sapiens) RGD 
SufuRatHedgehog signaling pathway   ISOSUFU (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Dhh  (desert hedgehog signaling molecule)
Gli1  (GLI family zinc finger 1)
Gli2  (GLI family zinc finger 2)
Gli3  (GLI family zinc finger 3)
Ihh  (Indian hedgehog signaling molecule)
Ptch1  (patched 1)
Shh  (sonic hedgehog signaling molecule)
Smo  (smoothened, frizzled class receptor)
Sufu  (SUFU negative regulator of hedgehog signaling)

Genes (Mus musculus)
Dhh  (desert hedgehog)
Gli1  (GLI-Kruppel family member GLI1)
Gli2  (GLI-Kruppel family member GLI2)
Gli3  (GLI-Kruppel family member GLI3)
Hhat  (hedgehog acyltransferase)
Ihh  (Indian hedgehog)
Ptch1  (patched 1)
Ptch2  (patched 2)
Shh  (sonic hedgehog)
Smo  (smoothened, frizzled class receptor)
Sufu  (SUFU negative regulator of hedgehog signaling)

Genes (Homo sapiens)
DHH  (desert hedgehog signaling molecule)
GLI1  (GLI family zinc finger 1)
GLI2  (GLI family zinc finger 2)
GLI3  (GLI family zinc finger 3)
HHAT  (hedgehog acyltransferase)
IHH  (Indian hedgehog signaling molecule)
PTCH1  (patched 1)
PTCH2  (patched 2)
SHH  (sonic hedgehog signaling molecule)
SMO  (smoothened, frizzled class receptor)
SUFU  (SUFU negative regulator of hedgehog signaling)


Additional Information