Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, 550001, Guiyang, China.
College of Clinical Medicine, Guizhou Medical University, 550001, Guiyang, China.
Cell Death Dis. 2023 Oct 24;14(10):699. doi: 10.1038/s41419-023-06207-y.
Pancreatic cancer (PC), a gastrointestinal tract malignant tumor, has a poor prognosis due to early metastasis and limited response to chemotherapy. Therefore, identifying novel therapeutic approaches for PC is critical. Epithelial-mesenchymal transition (EMT) is known as the vital progress in PC development, we constructed the EMT-related prognosis model to screen out that FOXQ1 probably involving in the EMT regulation. FOXQ1 has been linked to the malignant process in a number of cancers. However, its function in PC is unknown. In our work, the expression of FOXQ1 was elevated in PC tissues, and a high level of FOXQ1 in PC was linked to patients' poor prognosis. FOXQ1 overexpression promoted aerobic glycolysis and enhanced PC cell proliferation, tumor stemness, invasion, and metastasis. Whereas, FOXQ1 silencing showed the reverse effect. Furthermore, mechanistic studies indicated that FOXQ1 promotes LDHA transcription, and thus modulates aerobic glycolysis to enhance PC cell proliferation, tumor stemness, invasion, and metastasis by increasing LDHA expression. Therefore, these novel data suggest that FOXQ1 may be a possible therapeutic target in PC.
胰腺癌（PC）是一种胃肠道恶性肿瘤，由于早期转移和对化疗的反应有限，预后较差。因此，寻找 PC 的新治疗方法至关重要。上皮-间充质转化（EMT）是 PC 发展的重要过程，我们构建了 EMT 相关的预后模型，筛选出 FOXQ1 可能参与 EMT 调节。FOXQ1 已与多种癌症的恶性过程有关。然而，其在 PC 中的功能尚不清楚。在我们的工作中，FOXQ1 在 PC 组织中表达上调，PC 中高水平的 FOXQ1 与患者预后不良相关。FOXQ1 过表达促进有氧糖酵解并增强 PC 细胞增殖、肿瘤干性、侵袭和转移。然而，FOXQ1 沉默则显示出相反的效果。此外，机制研究表明，FOXQ1 促进 LDHA 转录，从而通过增加 LDHA 表达来调节有氧糖酵解，增强 PC 细胞增殖、肿瘤干性、侵袭和转移。因此，这些新数据表明 FOXQ1 可能是 PC 的一个潜在治疗靶点。
