Knockdown of pancreatic adenocarcinoma upregulated factor (PAUF) suppresses proliferation, migration, invasion, and cancer stem cell properties in lung cancer cells

Abstract

Purpose: To investigate the role of pancreatic adenocarcinoma up-regulated factor (PAUF) in lung cancer. Method: Proliferation of lung cancer cell lines (A549 and H1299) was determined using MTS and Edu staining assays. Wound healing and transwell assays were performed to evaluate cell migration and invasion abilities. Lung cancer stem cell (CSC) marker expressions, including CD133, CD44, ALDH1, SOX2, and Oct4, were determined by western blot assay. Results: Knockdown of PAUF significantly inhibited A459 and H1299 cell proliferation (p < 0.01). The wound healing and transwell assay results indicated that depletion of PAUF markedly suppressed H1299 and A549 cell migration and invasion, compared with the control cells (p < 0.01). Knockdown of PAUF reduced distinct CSC marker expression, suggesting inhibition of CSC phenotypes, and reduced phosphorylated focal adhesion kinase (FAK), phosphorylated Src, and phosphorylated extracellular signal-regulated kinase (ERK), but not total FAK, Src, and ERK. These results suggested that knockdown of PAUF deactivated the FAK/Src/ERK signal pathway. Conclusion: Knockdown of PAUF inhibits lung cancer cell proliferation, migration, invasion, and CSC properties via deactivation of FAK/Src/ERK signal pathway. These results may provide a novel strategy for the development of lung cancer therapeutics.