Epithelial mesenchymal transition and lung cancer

Abstract

Despite the therapeutic advances, lung cancer remains the leading cause of cancer-related death in the United States and worldwide. Metastasis and recurrence are considered to be responsible for the failure of treatment. Recent studies indicate Epithelial mesenchymal transition, an evolutionarily conserved process, plays an important role in the embryonic development and cancer progression and is involved in the metastasis, drug resistance and correlated with progression of many tumors. Of importance, EMT is also involved in the acquisition of stemness phenotype of tumor cells. Although a growing body of evidence supports the role of EMT in the progression of many cancers, and a number of signal pathways, transcriptional factors and microRNAs involved in EMT process have been identified. However, the role of EMT in lung cancer is elusive. In this review, we present the recent findings in EMT including the molecular mechanisms of EMT, and the involvement of EMT in cancer progression, cancer stem cells and drug resistance, especially focusing on the correlation of EMT and lung cancer.

Keywords: cancer stem cell; drug resistance; epithelial mesenchymal transition; lung cancer.

Fig 1.. Schematic of the signal transduction pathways associated with EMT. TGF-β is a major inducer of EMT. It binds to the receptors leading to the phosphorylation of Smad2 and Smad3. Activated Smad2 and Smad3 form trimers with Smad4, Smads complex are then translocated into nucleus where they associate and cooperate with DNA binding transcriptional factors such as Snail, ZEB and Twist to regulate the expression of TGF-β target genes, resulting in the downregualtion of epithelail markers and the upregualtion of mesenchymal markers. TGF-β also cooperates with other signal factors such as Wnt and growth factors that act through receptor tyrosine kinase to regulate EMT. Several microRNAs have been indentified to regulate EMT. miR-200 suppresses EMT mainly through targeting ZEB factors and ZEB factors also regulate the expression of miR-200 and miR-203, linking the EMT and stem maintenance of cancer stem cells.