TNFa and ZEB1 Contribute to Tumorigenesis in Chemo-Resistant Breast Cancer Cells

Abstract

Cancer genes are identified by their altered expression which induces uncommon phenotypic characteristics in a variety of cancers. The modified expression of these genes may promote the stimulation or development of a neoplasm, as oncogenes do, or may impede it, as do tumor suppressor genes. Breast cancer (BC) is the most prevalent malignancy in women and has been so over the past two decades. Comprehension of the biological pathways that lead to gene expression alterations and its association with therapy response is crucial for identifying novel biomarkers or mechanisms involved in therapy response. Analysis of a selection of genes regularly mis regulated in BC and associated with epithelial-mesenchymal transition (EMT), was performed utilizing the Cancer Genome Atlas (TCGA) and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) pathway analysis. Our results indicate upregulation of tumor necrosis factor a (TNFa) in chemo-sensitive and chemo-resistant BC cells, and upregulation of zinc finger E-box binding protein 1 (ZEB1) only in chemo-resistant cells. The gene expression alterations revealed by our cells also induced cellular proliferation upon chemotherapeutic treatment. Moreover, our results indicate that interaction between TNFa and ZEB1 encourages chemoresistance in BC cells. Being that TNFa and ZEB1 promote cell displacement and invasiveness through EMT stimulation, we herein propose that these genes employ such a pathogenic mechanism to render cells resistant to chemotherapeutic treatment. EMT is an overly complex, but also reversible event; therefore, further investigation of genes involved in the inhibition of TNFa and ZEB1 are an effective strategy for cancer therapy.