胰腺导管腺癌（PDAC）由于易于逃避早期发现、频繁转移以及随后设计有效治疗的挑战而构成重大威胁。 PDAC 中控制上皮间质转化 (EMT) 的过程有望推动新型治疗策略的发展。 SAMD1（含 SAM 结构域的蛋白 1）是一种 CpG 岛结合蛋白，在抑制其靶基因中发挥着关键作用。在这里，我们揭示了 SAMD1 作为 EMT 相关基因的抑制因子。在 PDAC 细胞中删除 SAMD1 后，我们观察到迁移率显着增加。 SAMD1 通过与特定基因组靶标（包括编码 N-钙粘蛋白的 CDH2）结合来发挥作用，CDH2 在 SAMD1 敲除后成为增强迁移的驱动因素。此外，我们发现含有 FBXO11 的 E3 泛素连接酶复合物作为 SAMD1 的相互作用子和负调节因子，在全基因组范围内抑制 SAMD1 染色质结合。 PDAC 中 FBXO11 高表达与预后不良和 EMT 相关基因表达增加相关，强调了 SAMD1 和 FBXO11 之间的拮抗关系。总之，我们的研究结果提供了对 PDAC 中 EMT 相关基因调控的见解，揭示了 SAMD1 的复杂作用及其与 FBXO11 在这种癌症类型中的相互作用。版权所有：© 2024 Simon 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Pancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with EMT. Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin-binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.Copyright: © 2024 Simon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.