Open Access Dissertation
Date of Award
Obesity is a risk factor for both TNBC and PCa, and pro-inflammatory features associated with obesity, including upregulated production of ROS, promote CSCs. Previously published work from the Bollig-Fischer laboratory established that TNBC CSCs could be inhibited by neutralizing ROS in culture with H2O2 targeted antioxidants. In this report, antioxidant treatment resulted in the downregulation of mRNA splicing variant MBD2_v2. MBD2_v2 was highly expressed in CSCs versus bulk TNBC cells and supported self-renewal in vitro. As obesity is coupled with increased ROS, we hypothesized that obesity could drive CSCs via MBD2_v2 expression. The work presented in this thesis addressed this hypothesis, linking MBD2_v2 expression to obesity in TNBC patients, and demonstrating the importance of SRSF2-MBD2_v2 mediated expression of pluripotency transcription factors in driving tumor-initiating TNBC CSCs via DIO and PCa CSCs via STAT3-dependent IL-6 signaling.
Teslow, Emily A., "Investigation Of The Role For Methyl-Cpg Binding Protein 2 Variant Mbd2_v2 In Cancer Stem Cells And Obesity-Associated Cancers" (2019). Wayne State University Dissertations. 2246.