Pathways (Hh, Metastatic cascade, Ubiquitin proteasome, clotting cascade) Flashcards
Hedgehog
a signaling mechanisms which occurs in primary cilia, but also the skin (basal cell carcinoma)
Smoothened (SMO)
proto-concogene encoded by SMO gene
PTCH
tumour suppressor (PTCH 1 gene)
mutations in either SMO of PTCH can result in
basal cell carcinoma
roles in the cell of Hh signaling
- angiogenesis
- increase in cyclins and increase in cell division
- causes a decrease i apoptotic genes
Hh pathways stimulates
Int to produce Cyclin D and CDK 4/6
when Hh isn’t bound
1) PTCH sterically hinders SMO from translocating to the cilium
2) therefore it won’t move to the cilium and activate GLI
3) GLI remains in its repressed form and transcription doesn’t occur
when Hh is bound
1) causes PTCH and Hh complex to endocytose into the cell forming a vesicle which contains PTCH and Hh
2) this becomes a lysosome and is degraded
3) allowing SMO to translocate tot eh cilium
4) SMO activates GLI to GLI-A
5) GLI-A acts as a TF e.g.activating Wnt signalling
6) growth and development
mutations in SMO and PTCH 1 can cause
basal cell carcinoma
common to get mutations in PTCH 1 because
because its common to deactivate tumour suppressors and it is hard to activate photo-oncogenes
metastatic cascade
is the process in which tumour cells from primary cancer spread to other sites forming secondary cancers
which signaling pathways will help cause a tumour to growt
- HIF
- Wnt
- Hh
metastatic cascade
1) primary tumour proliferates and grows stimulating angiogenesis
2) please of a tumour cell from the tumour and invasion into basement membrane
3) tumour cell secret metalloprotinase (MMP) to breakdown ECM (collagen breakdown)
4) invasion into capillary and or lymph
5) evasion of immune system - has self antigens
6) Vcam-1 on tumour surface allows the cell to marginate along the endothelial wall and use secretions to force themselves through the pore
7) grows - secondary tumour
how many tumour cells successfully metastasise
0.01 %
