Department of Physics, Chemistry and Biology (IFM)

By inhibiting the Wnt pathway, our results have shown downregulation of:

► one ligand (JAG 2)

► one receptors (Notch 2)

► one transcriptional activator (MAML 1)

► two target genes (Hes 1, Hes 7)

► two inhibitors (NUMB, NUMBL)

► two of Notch glycosyltransferases (LFNG, RFNG)

 

►Is accomplished by the Tcf/Lef target gene pro gram, shown by transfecting the cells with siRNA against β-catenin.

 

►This total down regulation of the Notch pathway upon Wnt deactivation shows a correlation betwe en the two signaling pathways in colorectal cancer.   We did not find any correlation the other way around, between Notch inhibition and Wnt pathway through β-catenin signalling.

 

►Using gamma-secretase inhibitors may provide a targeted-drug strategy for treating human colorec tal cancer, because of the close correlation betwe en the Notch and Wnt pathway

 

►Inhibition of Notch signalling gives a decrease in Hes 1 gene expression, leading to halt of cell proli feration and generation of apoptosis.  

►Preclinical studies for Alzheimer’s disease in ro dents have shown that a side effect of gamma- secretase inhibitors is macroscopic abnormalities i n the GI-tract, where the small and large intestine is distended and with an excess of mucus

 

►This may be one way of inhibiting the upregulation of the Notch pathway in colorectal cancer.