Pin1 promotes pancreatic cancer progression and metastasis by activation of NF‐κB‐IL‐18 feedback loop

• DOI: 10.1111/cpr.12816
• Publication Date: 2020-04-29T10:18:05Z
• Authors: Qiqing Sun; Guixiong Fan; Qifeng Zhuo; Weixing Dai; Zeng Ye; Shunrong Ji; Wenyan Xu; Wensheng Liu; Qiangsheng Hu; Zheng Zhang; Mengqi Liu; Xianjun Yu; Xiaowu Xu; Yi Qin
• Keywords: 0301 basic medicine; Transcription, Genetic; Interleukin-18; NF-kappa B; Original Articles; 3. Good health; Gene Expression Regulation, Neoplastic; NIMA-Interacting Peptidylprolyl Isomerase; Pancreatic Neoplasms; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Disease Progression; Humans; Phosphorylation; Promoter Regions, Genetic; Pancreas; Cell Proliferation; Signal Transduction

Accumulated evidence suggests that Pin1 contributes to oncogenesis of diverse cancers. However, the underlying mechanism oncogenic function in PDAC requires further exploration.IHC was performed using tissues. Western blot, PCR, immunofluorescence and transwell were cell lines. GSEA applied for possible downstream pathways. ChIP assay dual luciferase used assessment transcriptional activity.Both IL-18 levels are increased primary tissues their positively correlated. High expression is a predictor poor prognoses. promoted pancreatic cancer proliferation motility by increasing expression, while knockdown also inhibited tumour-promoting effect IL-18. Both could enhance NFκB activity cells. When bound p65 protein, phosphorylation its nuclear translocation. In nucleus, simultaneously promoter enhanced transcription. addition, recruitment decreased Pin1-silenced cells.Our study improves understanding inflammation PDAC, which hallmark cancer; interacted with NF-κB signalling activation IL-18, continuously activating signalling, then forms positive feedback loop.