∆122p53 mice (a model of ∆133p53 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 null mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence and metastasis. We also show that ∆122p53 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 Δ133p53 activates 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 ∆133TP53 mRNA. Patients with elevated ∆133TP53 mRNA levels had a shorter disease-free survival. Our results suggest that ∆133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways, and that patients whose tumours have high ∆133TP53 may benefit from therapies targeting these pathways.

中文翻译：

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∆133p53亚型通过JAK-STAT和RhoA-ROCK信号传导的白细胞介素6激活促进肿瘤侵袭和转移。

∆122p53小鼠（∆133p53亚型的模型）易发肿瘤，具有广泛的炎症反应，血清IL-6升高。为了研究IL-6的作用，我们将Δ122p53小鼠与IL-6无效小鼠杂交。在这里，我们显示IL-6的减少减少了JAK-STAT信号传导，肿瘤发生率和转移。我们还显示，∆122p53激活RhoA-ROCK信号传导导致肿瘤细胞浸润，IL-6依赖性并可通过抑制JAK-STAT和RhoA-ROCK途径而降低。同样，我们显示Δ133p53激活了这些途径，在结肠直肠癌细胞中产生了侵袭性和迁移性表型。大肠肿瘤的基因表达分析表明，与Δ133TP53mRNA相关的GPCR信号丰富。∆133TP53 mRNA水平升高的患者的无病生存期较短。