Wnt Signalling Pathway Flashcards
How is wnt signalling implicated in type 2 diabetes?
Wnt signalling is involved in insulin sensitivity, so malfunctioning of this pathway could be involved in the development of T2DM.
Why may overexpression of Wnt5b lead to increased susceptibility of developing T2DM?
Wnt5b has a role in adipogenesis. Thus, may increase risk as obesity and type II diabetes have high comorbitity.
Wnt signalling is a strong activator of mitochondrial what?
Biogenesis. This leads to increased production of reactive oxygen species (ROS) known to cause DNA and cellular damage.
This ROS-induced damage is significant because it can cause acute hepatic insulin resistance, or injury-induced insulin resistance.
Why is the ROS-induced cellular damage, as a result of Wnts role as a strong activator of mitochondrial biogenesis, significant in potentially increasing the risk of developing T2 diabetes?
ROS-induced damage can cause acute hepatic insulin resistance or injury-induced insulin resistance.
Mutations in Wnt signalling-associated transcription factors are linked to increased T2 diabetes susceptibility. What is an example of one such transcription factor?
TCF 7L2
T-Cell Factor/Lymphoid enhancing factor.
TCL/LEF.
What is the Wnt pathway?
A proto-oncogene pathway mutated in 90% of colon cancer.
Normal somatic cells do not tend to use the Wnt pathway.
APC is a TSG: inhibits B-catenin.
Down regulation of the secreted Frizzled- related proteins (SFRPs), which are Wnt inhibitors, has been observed in breast cancers (Veeck et al. 2008)
Why has down regulation of the secreted Frizzled-related proteins (SFRPs) been observed in breast cancers? (Veeck et al. 2008)
They are inhibitors of the proto-oncogenic Wnt pathway which leads to cell proliferation.
Wnt + frizzled receptor –> break up of the degradation complex of B-catenin-APC-Axin-CK1-Gsk3.
B-catenin can translocate to the nucleus and displaces groucho from TCF, recruits pro-TF causing cyclin D and myc-c.
What is OMP-_____?
OMP-54F28: An antibody that targets five frizzled receptors.
It has been shown to decrease tumour cell proliferation and CSC numbers in lung, breast and pancreatic tumours.
Downsides to Wnt targetting: concerns over whether the wnt pathway is instrinsic in fundamental biological process including tissue homeostasis and repair.
