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Summary: Tumorbio-8
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1 Tumorbio-8
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What is dukes classification of CRC?
A = cancer is confirmed to the lining of the colon
B = cancer has penetrated the colon wall
C = cancer has spread to lymph nodes
D = cancer has spread to other organs -
What is the effect of APC?
function of a scaffolding protein (GATEKEEPER) -> affecting cell-adhesion and migration segregation -
What is the effect of the WNT signalling pathway?
phosphorylation or degradation of beta-catenin -
What happens when APC is mutated in WNt siganlling?
beta-catenin binds to the TCF family of TFs, altering the expression of various genes affecting different processes in the colonic crypt -
What is the effect of inactivation of APC?
chromosome instability -> defects in mitotic spindles and chromosome missegregated -> aneuploidy -> cancer -
What is in the destruction complex for WNT?
APC, axin, GSK3, casein kinase I -
What is the effect of the destruction complex?
phosphorylation beta-catenin -> polybiquinated by E3 ligase TrCP -> proteasome degrades Bcat -
What is the effect of TCF proteins?
block degradation of Bcatenin by the proteasome -
What is canonical model fpr Wnt regulation?
ligand bind LRP5/6 -> axin binding site -> inactivates the destruction complex -> Bcat stabiel -> displaced groucho from TCF -> Bcat + TCF -> transcriptie in crypt stem cells -
What is the effect of mutations in CTNNB1?
no phosphorylation of Bcatenin -> no degradation -> transcription!
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