HealthValue
The NOTCH pathway
In 1919 Thomas Hunt Morgan laid the ground for all our knowledge on Drosophila melanogaster in his book The Physical Basis of Heredity. Above are his drawings of "notched" abnormal wings.
Binding of ligands (DLL4 delta like ligand 4, or Jagged 1) to EGF repeats of Notch receptor triggers downstream cleavages, which lead to activation of transcription factors
Notch
can
act
as
an
oncogene,
a
tumor
suppressor,
a cell differentiation agent
Notch receptors can be involved in ubiquitous phenomena :
- blockade of DLL4 induces formation of excessive neovasculature, choking tumors
rather than feeding them;
- notch receptors can be downregulated in basal cells carcinomas, ditto cervical cancers (notch signaling counteracts HPV);
- in mice Notch signals can inhibit tumor formation;
- Notch 3 receptor (there are 4 notch receptors) is overexpressed in 20% of ovary cancers;
- a gain of function of Notch 1 is associated with acute T cell leukemia;
- overexpression of Notch 4 is met with in mice breast cancer;
- inhibition of Notch signaling can curb differentiation of wnt induced colorectal cancer