鉴于溶酶体在细胞稳态中的重要作用，本研究重点关注溶酶体运输在前列腺癌中的作用。使用 LAMP-1 转染的前列腺细胞的共焦激光扫描显微镜和点跟踪分析评估溶酶体运动性。在患者队列数据库中并通过肿瘤样本的免疫组织化学评估溶酶体运输机制的表达。通过过表达和 siRNA 评估囊泡运输机制的作用。通过 RNA 测序、蛋白质定量以及固定细胞和活细胞显微镜评估 R1881 治疗对溶酶体囊泡运输的影响。在前列腺癌组织中观察到溶酶体运输基因/蛋白质的调节发生改变，与囊泡共表达具有显着相关性。格里森模式的贩运机器。贩运机制的表达与较差的患者预后相关。 R1881 治疗诱导激素敏感前列腺癌细胞中溶酶体分布、数量和溶酶体囊泡运输机制表达的变化。在非恶性和前列腺癌细胞中，对参与溶酶体运输事件的基因进行操作会引起溶酶体定位和细胞表型的变化，以及对细胞迁移的不同影响。这些发现为溶酶体囊泡的调节改变和功能影响提供了新的见解。前列腺癌发病机制中的贩运。© 2024。作者。

This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis.Lysosomal motility was evaluated using confocal laser scanning microscopy of LAMP-1-transfected prostate cells and spot-tracking analysis. Expression of lysosomal trafficking machinery was evaluated in patient cohort databases and through immunohistochemistry on tumour samples. The roles of vesicular trafficking machinery were evaluated through over-expression and siRNA. The effects of R1881 treatment on lysosome vesicular trafficking was evaluated by RNA sequencing, protein quantification and fixed- and live-cell microscopy.Altered regulation of lysosomal trafficking genes/proteins was observed in prostate cancer tissue, with significant correlations for co-expression of vesicular trafficking machinery in Gleason patterns. The expression of trafficking machinery was associated with poorer patient outcomes. R1881 treatment induced changes in lysosomal distribution, number, and expression of lysosomal vesicular trafficking machinery in hormone-sensitive prostate cancer cells. Manipulation of genes involved in lysosomal trafficking events induced changes in lysosome positioning and cell phenotype, as well as differential effects on cell migration, in non-malignant and prostate cancer cells.These findings provide novel insights into the altered regulation and functional impact of lysosomal vesicular trafficking in prostate cancer pathogenesis.© 2024. The Author(s).