EGR1 induces EMT in pancreatic cancer via a P300/SNAI2 pathway

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.