HSP70 Promotes Pancreatic Cancer Cell Epithelial-Mesenchymal Transformation and Growth Via the NF-κB Signaling Pathway

ObjectiveTo study the effects of HSP70 on proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) of pancreatic cancer cells and explore its underlying mechanisms.MethodsPancreatic cancer cell models with reduced HSP70 or increased HSP70 expression were established. Reverse transcription quantitative polymerase chain reaction and Western blot assays were used to determine mRNA and protein levels of HSP70, IKK/I kappa Ba/NF-kappa B signaling pathway-related genes, and EMT markers. CCK-8 and cell cloning assays were used to evaluate cell proliferation and cloning abilities. Transwell and wound healing assays were used to assess the invasive and migratory properties of cells. Electrophoresis mobility shift assay (EMSA) and luciferase reporter assays were conducted to analyze NF-kappa B's promoter binding and transcriptional activities.ResultsHSP70 knockdown inhibited p-p65 nuclear translocation, the expression of p-p65, p-IKK alpha/beta, p-I kappa B alpha, N-cadherin, Vimentin and Twist, NF-kappa B's promoter binding and transcriptional activities, pancreatic cancer cell proliferation, cloning, migration and invasion, while increased E-cadherin levels. HSP70 overexpression took the opposite effects. NF-kappa B signaling pathway modulation reversed EMT changes induced by altered HSP70 expression levels. rhHSP70 increased p-IKK alpha/beta and p-I kappa B alpha protein levels.ConclusionsHSP70 promotes EMT and enhances pancreatic cancer cell proliferation, migration, and invasion by activating NF-kappa B pathway.