EGR1 regulates IGF-1-stimulated pancreatic cancer cell invasion by increasing IL-11 expression.

Interleukin-11 (IL-11), a member of the glycoprotein-130 cytokine family, has been implicated in inflammation-associated malignancies, including pancreatic cancer, where both IL-11 and its receptors are frequently overexpressed; however, the transcriptional mechanisms that regulate IL-11 expression remain unclear. To investigate this mechanism, promoter reporter assays, electrophoretic mobility shift assays, EGR1 knockdown experiments, gene expression analyses and three-dimensional spheroid invasion assays were performed in pancreatic cancer cells. In the present study, early growth response 1 (EGR1) was identified as a key regulator of insulin-like growth factor 1 (IGF-1)-induced IL11 transcription. Promoter analyses revealed a conserved EGR1-binding sequence (EBS) within the proximal IL11 promoter that is essential for IGF-1-responsive transcriptional activation. Electrophoretic mobility shift assays demonstrated that EGR1 directly binds to this site. Functional silencing of EGR1 markedly attenuated IGF-1-induced IL-11 expression and reduced invasive behavior in a three-dimensional pancreatic cancer spheroid model. Collectively, these findings delineated an IGF-1/EGR1/IL-11 signaling axis linking growth factor-dependent transcriptional regulation to invasive phenotypes and highlighted a potential therapeutic target in pancreatic cancer.