This article seeks to understand the relationship between the transcription factor Ets-1 and cancer progression. To do this, they test whether Ets-1 activation leads to the expression of MMP-9, a matrix remodeling protein that degrades extracellular components to facilitate tissue invasion in carcinoma. They found this to be the case when reducing expression of Ets-1 and observing a decrease in expression of MMP-9.
Then, they wanted to see if knockdown (KD) of Ets-1 would have any effect on invasion and expression of markers for epithelial-mesenchymal transition, key regulators of cancer metastasis. They performed Transwell invasion assays to assess the proficiency of carcinoma to cross across a barrier when treated with the Ets-1 inhibitor. They found that KD cells invaded in fewer numbers compared to wild type (WT), and that EMT markers were downregulated in metastatic breast cancer.
Following, they wanted to see if there were any direct interactions between Ets-1 and the promoter region of MMP-9 that would induce its expression. They performed a chromatin immunoprecipitation experiment in which they select protein-DNA interactions and then search for the specific protein of interest and digest the rest. They found that there is in fact direct binding between the transcription factor and the promoter region the metalloprotease.
In short, they found a direct correlation between Ets-1 activity and MMP-9 expression. They found that inhibition of Ets-1 directly causes a decrease in the aggressive phenotypes of breast cancer. Additionally, they found a direct DNA-protein interaction between the transcription factor and metalloprotease.
Citations:
Nazir, S. et al. “Breast cancer invasion and progression by MMP-9 through Ets-1 transcription factor”. Gene. 2019 Aug 30; 711:143952
https://pubmed.ncbi.nlm.nih.gov/31265880/