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 General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
J Transl Med. 2023 Mar 17;21(1):201. doi: 10.1186/s12967-023-04043-4.
The prognosis of pancreatic cancer patients remains relatively poor. Although some patients would receive surgical resection, distant metastasis frequently occurs within one year. Epithelial-mesenchymal transition (EMT), as a pathological mechanism in cancer progression, contributed to the local and distant metastasis of pancreatic cancer.
Tissue microarray analysis and immunohistochemistry assays were used to compare the expression of EGR1 in pancreatic cancer and normal pancreatic tissues. Transwell chambers were used to evaluated the migration and invasion ability of cancer cells. Immunofluorescence was utilized to assess the expression of E-cadherin. ChIP-qPCR assay was applied to verify the combination of EGR1 and SNAI2 promoter sequences. Dual-luciferase reporter assay was used to detect the gene promoter activation. Co-IP assay was conducted to verify the interaction of EGR1 and p300/CBP.
EGR1 was highly expressed in pancreatic cancer rather than normal pancreatic tissues and correlated with poor prognosis and cancer metastasis. EGR1 was proved to enhance the migration and invasion ability of pancreatic cells. Besides, EGR1 was positively correlated with EMT process in pancreatic cancer, via a SNAI2-dependent pathway. P300/CBP was found to play an auxiliary role in the transcriptional activation of the SNAI2 gene by EGR1. Finally, in vivo experiments also proved that EGR1 promoted liver metastasis of pancreatic cancer.
Our findings implied the EMT-promoting effect of EGR1 in pancreatic cancer and revealed the intrinsic mechanism. Blocking the expression of EGR1 may be a new anticancer strategy for pancreatic cancer.
胰腺癌患者的预后仍然较差。尽管一些患者会接受手术切除，但远处转移通常在一年内发生。上皮间质转化（EMT）作为癌症进展的病理机制，促进了胰腺癌的局部和远处转移。
使用组织微阵列分析和免疫组织化学检测比较 EGR1 在胰腺癌和正常胰腺组织中的表达。Transwell 室用于评估癌细胞的迁移和侵袭能力。免疫荧光用于评估 E-钙黏蛋白的表达。ChIP-qPCR 检测用于验证 EGR1 和 SNAI2 启动子序列的结合。双荧光素酶报告基因检测用于检测基因启动子的激活。Co-IP 检测用于验证 EGR1 和 p300/CBP 的相互作用。
EGR1 在胰腺癌中高表达，而在正常胰腺组织中低表达，与不良预后和癌症转移相关。EGR1 被证明增强了胰腺细胞的迁移和侵袭能力。此外，EGR1 通过 SNAI2 依赖性途径与胰腺癌中的 EMT 过程呈正相关。发现 p300/CBP 在 EGR1 对 SNAI2 基因的转录激活中起辅助作用。最后，体内实验也证明 EGR1 促进了胰腺癌的肝转移。
我们的研究结果表明 EGR1 在胰腺癌中具有促进 EMT 的作用，并揭示了内在机制。阻断 EGR1 的表达可能是一种新的胰腺癌治疗策略。
