Metastasis is associated with poor prognosis and is the major cause of death in cancer patients. The epithelial to mesenchymal transition (EMT) is essential for cancer cells to acquire a highly migratory phenotype. Metabolic reprogramming is required to meet the energy demands during this process. Recent studies have indicated that autophagy is involved in EMT, during which cancer cells depend on autophagy activation for survival. However, accumulating evidence indicates that autophagy's involvement in cancer is context-dependent, acting as either promoter or inhibitor. In this study, we investigated the role of autophagy in supplying energy to support EMT. We induced EMT in Non-small cell lung cancer A549 cells using TGF-β1 with and without autophagy inhibition. Suppression of autophagy activity by knocking down of BECN1 or chloroquine (CQ) treatment inhibited mesenchymal protein expression. Interestingly, TGF-β1 promoted the transcription of target mRNAs, SNAI1, VIM, and CDH2, regardless of autophagy status. The imbalance between protein and mRNA levels indicated the possibility of autophagy-dependent translational regulation. Since protein synthesis consumes large amounts of energy, it is tightly regulated via various cellular signaling pathways such as AMPK and mTOR. Our investigation showed inhibition of autophagy decreased ATP production from OXPHOS and led to the suppression of mRNA translation by phosphorylation of eukaryotic elongation factor 2 (eEF2). These results suggest that A549 non-small cell lung cancer required autophagy to maintain mitochondrial homeostasis during TGF-β1 induced EMT. In conclusion, blocking autophagy decreased energy production and down-regulated proteins synthesis inhibiting TGF-β1 induced EMT.
Keywords: A549 cells; EMT; TGF-β1; autophagy; energy metabolism.