Gene expression data from colorectal cancers

D122p53 mice (a model of D133p53 isoform) are tumour prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed 122p53 mice with IL-6 deficient mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence, and metastasis. We also show that D122p53 activates RhoA-ROCK signalling leading to tumour cell invasion which is IL-6 dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that 133p53 activates the these pathways, resulting in invasive and migratory phenotypes, in colorectal cancer cells. Gene expression analysis of colorectal tumours showed enrichment of GPCR signalling associated with D133TP53 mRNA. Patients with elevated D133TP53 mRNA levels had a shorter disease free survival. Our results suggest that D133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways and that patients whose tumours have high D133p53 may benefit from therapies targeting these pathways.

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Campbell H, Fleming N, Roth I, Mehta S, Wiles A, Williams G, Vennin C, Arsic N, Parkin A, Pajic M, Munro F, McNoe L, Black M, McCall J, Slatter TL, Timpson P, Reddel R, Roux P, Print C, Baird MA, Braithwaite AW