丝氨酸蛋白酶抑制剂肽酶抑制剂进化枝 A 成员 1 (SERPINA1) 在多种实体瘤中高表达。然而，其在胰腺导管腺癌（PDAC）中的作用仍不清楚。在这里，我们报告了 SERPINA1 作为一种强癌基因来驱动其极端恶性特征的证据。我们发现原发肿瘤中 SERPINA1 表达升高与 PDAC 患者的淋巴结转移和较短的生存期相关。机制研究表明，SERPINA1的过表达通过PI3K/Akt/NF-κB通路诱导p65亚基的核转位和磷酸化，从而促进PDAC细胞体内外的侵袭、转移和增殖。相反，SERPINA1 的敲除减弱了该信号通路并恢复了过表达 SERPINA1 的 PDAC 细胞的表型。总体而言，我们的研究揭示了 SERPINA1 通过 PI3K/Akt/NF-κB 通路影响 PDAC 的特性，其激活赋予了疾病中上皮间质转化和增殖的临床特征。版权所有 © 2024。由 Elsevier Inc. 出版。

Serpin peptidase inhibitor clade A member 1 (SERPINA1) is highly expressed in a variety of solid tumors. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we report evidence that SERPINA1 acts as a potent oncogene to drive its extremely malignant character. We found that elevated SERPINA1 expression in primary tumors was associated with lymph node metastasis and shorter survival in PDAC patients. Mechanistic investigations revealed that overexpression of SERPINA1 induced nuclear translocation and phosphorylation of the p65 subunit through the PI3K/Akt/NF-κB pathway, thereby promoting the invasion, metastasis and proliferation of PDAC cells in vitro and in vivo. Conversely, the knockdown of SERPINA1 attenuated this signaling pathway and restored the phenotype of PDAC cells overexpressing SERPINA1. Overall, our study reveals that SERPINA1 affects the properties of PDAC through the PI3K/Akt/NF-κB pathway, and its activation confers the clinical features of epithelial-mesenchymal transition and proliferation in the disease.Copyright © 2024. Published by Elsevier Inc.