Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Cell Oncol (Dordr). 2024 Aug;47(4):1253-1265. doi: 10.1007/s13402-024-00925-x. Epub 2024 Mar 27.
Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms.
We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/β-catenin pathway.
We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/β-catenin signaling, and that a Wnt/β-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells.
Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/β-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.
先前的研究表明，干扰素诱导蛋白具有四肽重复序列 1（IFIT1）可促进癌症的发展。在这里，我们旨在探讨 IFIT1 在胰腺癌发生和发展中的作用，包括其潜在的机制。
我们使用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据集来研究 IFIT1 在胰腺癌样本中的表达。通过细胞计数试剂盒-8（CCK8）、集落形成、划痕愈合和 Transwell 测定来评估胰腺癌细胞的增殖、迁移和侵袭能力。通过基因集富集分析（GSEA）和 Western blot 来评估 IFIT1 对 Wnt/β-catenin 通路的调控作用。
我们发现 IFIT1 表达的上调在胰腺癌中很常见，且与患者总生存率呈负相关。IFIT1 表达的下调导致胰腺癌细胞的增殖、迁移和侵袭减少。我们还发现 IFIT1 可以调节 Wnt/β-catenin 信号通路，而 Wnt/β-catenin 激动剂可以逆转这种作用。此外，我们发现 IFIT1 可以促进胰腺癌细胞的上皮-间充质转化（EMT）。
我们的数据表明，IFIT1 通过激活 Wnt/β-catenin 通路增加胰腺癌细胞的增殖、迁移和侵袭。此外，我们发现 EMT 可以受 IFIT1 调节。IFIT1 可能成为胰腺癌的一个潜在治疗靶点。
