The epithelial-to-mesenchymal transition (EMT) is a critical mechanism during the process of normal embryonic development and wound healing that can be pathologically re-activated during cancer progression. We hypothesized that comparing the transcriptional programs of multiple EMT-driving transcription factors (EMT-TFs) would identify a common set of critical EMT effectors. After elucidating this common transcriptional program, the commonly upregulated RNA binding protein RBMS3 was chosen as a target for functional validation. RBMS3 was both necessary and sufficient for EMT and breast cancer progression, demonstrating the validity of focusing on common EMT-associated effectors. Finally, by evaluating the associations of multiple EMT-TFs with the tumor microenvironment in several solid tumor types, ZEB1 and a ZEB1-regulated transcription program was identified as uniquely associated with immune suppression and poor prognosis. In conclusion, this study significantly advances both the understanding of the mechanisms underlying EMT and the distinct associations of different EMT-TFs with tumor biology and the tumor microenvironment.
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:27741360 |
| Date | 01 January 2022 |
| Creators | Block, C. James Garnet |
| Publisher | Wayne State University |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
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