Curcumin suppresses the stemness of non‐small cell lung cancer cells via promoting the nuclear‐cytoplasm translocation of TAZ

Curcumin has been shown to suppress the progression of lung cancer, however, the underlying mechanisms are largely unknown. Here, we aimed to investigate the effects of curcumin on the stemness of non‐small cell lung cancer (NSCLC) cells. We found that curcumin reduced the sphere formation ability at the concentrations without affecting the cell viability of NSCLC cells and normal pulmonary epithelial cells, which is evident by the decrease of sphere size and number. In addition, curcumin decreased ALDH activity and the expression of stemness markers (CD133, EpCAM, Oct4). RNA sequencing analysis revealed that the Hippo pathway was mostly enriched in cells with curcumin treatment. Indeed, the expression of cancer stem cell markers was significantly decreased by curcumin treatment by analyzing the RNA sequencing data. Gene set enrichment analysis (GSEA) showed that curcumin negatively regulated the cancer stem cell function and positively modulated cancer stem cell differentiation ability. Furthermore, curcumin enhanced the cisplatin sensitivity of NSCLC cells. Mechanistically, it was found that curcumin promoted the nuclear‐cytoplasm translocation of TAZ, but not YAP, the critical effectors of Hippo pathway. In addition, curcumin destabilzed TAZ protein stability and promoted TAZ protein degradation in lung cancer cells, which is dependent on the proteasome degradation system, not by autophagy lysosome degradation system. Overexpression of TAZ rescued the inhibition of curcumin on the stemness of lung cancer cells. Thus, our results suggest that curcumin can attenuate the stemness of lung cancer cells through promoting TAZ protein degradation and thus activating Hippo pathway.