TGF- -Induced Epithelial-to-Mesenchymal Transition

Epithelial-to-mesenchymal transition (EMT) is the cancer-associated process wherein an epithelial cell converts into a mesenchymal type cell. Mesenchymal cells lack apical polarity and secrete extracellular-matrix-degrading enzymes that provide them with enhanced migration capabilities. Moreover, EMT is closely related to cancer stem cell-like phenotype mutations, such as chemotherapy resistance and enhanced survival when deprived of nutrients. Thus, it should not come as a surprise that EMT has been linked as a promoter of cancer metastasis and is of clear medical relevance. Multiple factors may activate an EMT state in a cell; one of the most successful promoters is the transforming growth factor(TGF). Presence of TGFinduces several changes in transcription and translation regulation within the cell. In particular, the production of the transcription factor SNAIL1 is upregulated upon increased TGFlevels; SNAIL1, in turn, influences levels of transcription factors ZEB1, TWIST, and SNAIL2 (SLUG), among others. The overall e↵ects of TGFtend towards increased repression of E-cadherin, a key marker of epithelial cells, and upregulation of N-caderin, a key marker of mesenchymal cells. As Tian, et al., have reported a model investigating the e↵ects of these transcription factors on E-cadherin and N-cadherin levels (2013), this report aims to further this model by incorporating the e↵ects of TWIST and SLUG transcription factors. In addition to influencing EMT through regulation of E-cadherin and N-cadherin, TWIST has also been shown to upregulate the production of endogenous TGF, further driving EMT. Additionally, TWIST increases SLUG production, which competes with the negative feedback system of ZEB1. By examining the influence of these two additional transcription factors on the previously reported system, this study will provide an interesting insight into how cancer is able to progress through EMT and shed light on therapeutic procedures relevant to cell migration, such as cancer metastasis.