P53 & its mutants in tumour cell migration and invasion (paper)

Question 1

who wrote this paper and when?

Answer 1

Muller at al in 2011

Question 2

what does a loss of P53 influence?

Answer 2

• influence cell cycle checkpoints and apoptosis

Question 3

what gene encodes P53?

Answer 3

TP53

Question 4

what phenotype to do with invasion and metastasis does loss of P53 look like?

Answer 4

EMT like

Question 5

what usually supresses levels of P53?

Answer 5

• E3 ubiquitin ligase - MDM2

Question 6

what can aleviate expression of P53 by MDM2?

Answer 6

-genotoxic/cellular stress (caused by DNA damage or oncogene signa;ing) can eleviate suppression of P53 which results in P53 stabilisation

Question 7

What proteins can down regulate molecules involved in the stabilisation cell-cell junctions e.g. e-cadherin?

Answer 7

Slug snail and twist proteins

Question 8

what do slug/snail and twist upregulate?

Answer 8

components of the migratory machinary to become invasive

Question 9

what does P53 expression promote MDM2 to degrade?

Answer 9

slug protein (loss of e-cadherin often seen in cancers - loss of epithelial cell genes - P53 cannot cause degradation of slug - slug downregulates e-cadherin)

Question 10

give the epistatic hierachy of twist, P53, slug and e-cadherin

Answer 10

Twist –| P53 –| slug –| e-cadherin

Question 11

what genes are upregulated when P53 is lost?

Answer 11

genes associated with an elongated mesenchymal migratory phenotype

Question 12

How does P53 GOF drive ivasion?

Answer 12

Drives invasion by inhibiting P63/P73

mutant P53s interact with P63 and P73 to negatively regulate their function