胰管腺癌（PDAC）具有隐匿性和高度恶性特征，预后极差，对目前化疗药物存在药物耐受性。因此，有迫切需要研究PDAC进展的分子机制，以开发有前途的诊断和治疗干预措施。同时，涉及膜蛋白的分拣、转运和定位的液泡蛋白分拣（VPS）蛋白已逐渐引起癌症研究人员的关注。虽然已有研究报道VPS35促进癌症进展，但其具体分子机制仍不清楚。在此，我们确定了VPS35对PDAC肿瘤发生的影响，并探讨了其潜在的分子机制。我们使用来自GTEx（对照）和TCGA（肿瘤）的RNAseq数据对46个VPS基因进行了全癌分析，并通过富集分析预测了VPS35在PDAC中的潜在功能。此外，我们通过细胞克隆实验、基因敲除、细胞周期分析、免疫组化和其他分子和生化实验，验证了VPS35的功能。结果表明，VPS35在多种癌症中高表达且与PDAC的不良预后有关。与此同时，我们证实VPS35能够调节细胞周期并促进PDAC中的肿瘤细胞生长。因此，我们提供了充分的证据表明，VPS35作为PDAC临床治疗的关键新靶点，能够促进细胞周期进程。 © 2023年作者授予Springer-Verlag GmbH Germany专属许可，隶属于Springer Nature。

Pancreatic ductal adenocarcinoma (PDAC) is insidious and highly malignant with extremely poor prognosis and drug resistance to current chemotherapies. Therefore, there is a critical need to investigate the molecular mechanism underlying PDAC progression to develop promising diagnostic and therapeutic interventions. In parallel, vacuolar protein sorting (VPS) proteins, involved in the sorting, transportation, and localization of membrane proteins, have gradually attracted the attention of researchers in the development of cancers. Although VPS35 has been reported to promote carcinoma progression, the specific molecular mechanism is still unclear. Here, we determined the impact of VPS35 on the tumorigenesis of PDAC and explored the underlying molecular mechanism. We performed a pan-cancer analysis of 46 VPS genes using RNAseq data from GTEx (control) and TCGA (tumor) and predicted potential functions of VPS35 in PDAC by enrichment analysis. Furthermore, cell cloning experiments, gene knockout, cell cycle analysis, immunohistochemistry, and other molecular and biochemical experiments were used to validate the function of VPS35. Consequently, VPS35 was found overexpressed in multiple cancers and correlated with the poor prognosis of PDAC. Meanwhile, we verified that VPS35 could modulate the cell cycle and promote tumor cell growth in PDAC. Collectively, we provide solid evidence that VPS35 facilitates the cell cycle progression as a critical novel target in PDAC clinical therapy.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.