∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling

• DOI: 10.1038/s41467-017-02408-0
• Publication Date: 2018-01-11T11:25:41Z
• Authors: Hamish Campbell; Nicholas Fleming; Imogen Roth; Sunali Mehta; Anna Wiles; Gail Williams; Claire Vennin; Nikola Arsic; Ashleigh Parkin; Marina Pajic; Fran Munro; Les McNoe; Michael Black; John McCall; Tania L. Slatter; Paul Timpson; Roger Reddel; Pierre Roux; Cristin Print; Margaret A. Baird; Antony W. Braithw...
• Keywords: Male; Science; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; Article; Disease-Free Survival; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Protein Isoforms; Neoplasm Invasiveness; RNA, Messenger; Neoplasm Metastasis; [SDV.BC] Life Sciences [q-bio]/Cellular Biology; Janus Kinases; rho-Associated Kinases; 0303 health sciences; Interleukin-6; Q; HCT116 Cells; Prognosis; 3. Good health; STAT Transcription Factors; Female; Tumor Suppressor Protein p53; Colorectal Neoplasms; Signal Transduction

Abstract ∆122p53 mice (a model of ∆133p53 isoform) are tumour-prone, have extensive inflammation and elevated serum IL-6. To investigate the role IL-6 we crossed with null mice. Here show that loss reduced JAK-STAT signalling, tumour incidence metastasis. We also activates RhoA-ROCK signalling leading to cell invasion, which is IL-6-dependent can be by inhibition pathways. Similarly, Δ133p53 these pathways, resulting in invasive migratory phenotypes colorectal cancer cells. Gene expression analysis tumours showed enrichment GPCR associated ∆133TP53 mRNA. Patients mRNA levels had a shorter disease-free survival. Our results suggest promotes invasion activation patients whose high may benefit from therapies targeting