TWF1 induces autophagy and accelerates malignant phenotype in lung adenocarcinoma via inhibiting the cAMP signaling pathway

Abstract

Many studies have shown that the actin cytoskeleton plays an essential role in the initiation and progression of cancer. As an actin-binding protein, Twinfilin1 (TWF1) plays an important role in regulating cytoskeleton-related functions. However, little is known about the expression and function of TWF1 in human tumors. The present study aimed to investigate the functional roles and the underlying molecular mechanisms of TWF1 in human lung adenocarcinoma (LUAD). By using bioinformatics databases and tumor tissues, TWF1 expression was found to be higher in LUAD tissues than in adjacent tissues and poor survival was predicted in patients with LUAD. In vitro and in vivo assays indicated that downregulation of TWF1 expression suppressed LUAD cells invasion and migration. Further studies revealed that TWF1 interacted with p62 and was involved in the regulation of autophagy. The molecular mechanisms underlying TWF1 were investigated by RNA-seq analysis and a series of functional experiments. The results showed that downregulation of TWF1 suppressed LUAD progression through the cAMP signaling pathway. Therefore, overexpression of TWF1 in LUAD promoted migration, invasion, and autophagy through the cAMP signaling pathway.