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Cooperation of ZEB1 and SNAI1 Transcription Factors in Induction of Epithelial to Mesenchymal Transition

Hanna Traggiai*, Emily Means, Pete Womack, Jessica Johnson and Alexey Ivanov, Department of Biochemistry and WVU Cancer Institute, School of Medicine, West Virginia University, Morgantown, WV 26506

Field (Broad Category): Biochemistry - Cancer/Cell/Molecular Biology (Health Sciences) 

Student’s Major: Biochemistry 

EMT is activated during cancer invasion, promotes metastasis and predicts poor patient outcome. The transcriptional network involved in the activation of EMT has been found to be governed by few transcription factors including ZEB1, SNAI1 (Snail), and TCF4. Previous research has shown in mesenchymal cell lines that although ZEB1 played the major role, multiple EMT transcription factors cooperated in induction of full EMT. This research investigated individual and combinatorial roles of ZEB1, SNAI1 and TCF4 in induction of EMT in luminal epithelial cells. These three EMT-TFs were overexpressed separately and in combination, in T47D breast cancer cells and then their expression of EMT markers was analyzed by Western blotting. Individually SNAI1 and ZEB1 activated only partial EMT and decreased cell proliferation, while expression of both led to much stronger EMT and stimulation of cell growth. Interestingly, when expressed separately, the EMT-TFs induced expression of cyclin dependent kinase (CDK) inhibitor proteins including p21/CDKN1A, p27/CDKN1B and p14ARF. However, expression of ZEB1 and SNAI1 together led to downregulation of p21 and p27, consistent with increased cell proliferation. These results suggest that the EMT program is likely orchestrated by combined action of several EMT-TFs. 

Funding: 

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course