我们之前已经表明，S100P 结合伴侣 S100PBP 的表达在胰腺导管腺癌 (PDAC) 的进展过程中逐渐降低。在这里，我们发现 S100PBP 的缺失会导致胰腺细胞的致癌转化； S100PBP 表达失调后，计算机模拟和体外分析都强调了已知调节细胞骨架、细胞运动和存活的基因的改变。 S100P 的过表达降低了 S100PBP 的表达，而免疫共沉淀表明 S100P 与 S100PBP-p53-泛素蛋白复合物相互作用，可能导致 S100PBP 降解。多西环素诱导的 KrasG12D 激活导致 S100PBP 水平降低，而 HDAC 抑制剂 MS-275 的低剂量治疗可挽救其在人和小鼠 PDAC 细胞系中的表达。这表明 KrasG12D 是 S100PBP 的上游表观遗传调节因子。最后，对 TCGA PanCancer Atlas PDAC 数据集的分析表明，高 S100P 和低 S100PBP 表达的患者预后较差，表明 S100PBP 是一种具有潜在临床实用性的新型抑癌基因。© 2023。作者。

We have previously shown that expression of S100PBP, an S100P binding partner, gradually decreases during progression of pancreatic ductal adenocarcinomas (PDAC). Here, we show that loss of S100PBP leads to oncogenic transformation of pancreatic cells; after deregulation of S100PBP expression, both in silico and in vitro analyses highlighted alterations of genes known to modulate cytoskeleton, cell motility and survival. Overexpression of S100P reduced S100PBP expression, while co-immunoprecipitation indicated the interaction of S100P with S100PBP-p53-ubiquitin protein complex, likely causing S100PBP degradation. The doxycycline-induced KrasG12D activation resulted in decreased S100PBP levels, while low-dose treatment with HDAC inhibitor MS-275 rescued its expression in both human and mouse PDAC cell lines. This indicates KrasG12D as an upstream epigenetic regulator of S100PBP. Finally, analysis of TCGA PanCancer Atlas PDAC datasets demonstrated poor prognosis in patients with high S100P and low S100PBP expression, suggesting that S100PBP is a novel tumour suppressor gene with potential clinical utility.© 2023. The Author(s).