Early growth response factor 1 promotes HCC progression by activating the MAPK/ERK pathway through transcriptional upregulation of PAR1

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The prognosis of HCC patients who undergo surgical resection is still poor. Therefore, it is urgent to clarify the potential mechanism of HCC progression. This article reports the important role of the transcription factor early growth response 1 (Egr1) in promoting HCC progression. First, Egr1 expression was abnormally elevated in clinical HCC samples and enhanced the proliferation, invasion and migration of cancer cells. Moreover, we found that the mRNA expression levels of protease-activated receptor 1 (PAR1) and Egr1 in clinical specimens were positively correlated. Dual luciferase reporter gene assays verified that Egr1 is an upstream transcriptional regulator of PAR1, that enhances the proliferation, invasion and migration of cancer cells by upregulating PAR1. Mechanistically, we found that Egr1 activates the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway through PAR1. Finally, we demonstrated that thrombin does not affect the regulatory effect of Egr1 on PAR1 in HCC cells. In conclusion, Egr1 promotes HCC progression by upregulating PAR1 to activate the MAPK/ERK pathway.