SOX2 is Associated with Changes in DNA Damage Repair and Cell Cycle Gene Expression and Regulates E2F1

A leading cause of disease progression in prostate cancer patients is therapy resistance. As a result, different treatment schemes and combinations are employed to combat prostate cancer, advancing to more deadly prostate cancer. One mechanism that cancer cells utilize to evade treatment is through alterations in DNA damage repair pathways. Currently, the tumor expression profiles score for homologous recombination deficiency is available for patients. However, this is typically only used to determine if Poly (ADP-Ribose) Polymerase (PARP) inhibitors are an appropriate treatment option. One potential biomarker my lab has identified is SOX2. The expression of SOX2 was linked to an increased Gleason score at diagnosis and decreased time to metastasis after biochemical recurrence. Previously, SOX2 was found to promote lineage plasticity and resistance to AR-targeted therapies in prostate cancer. Further, the SOX2 protein is either present or absent in a prostate cancer tumor, making it an ideal biomarker. Our studies show that metastasis samples from prostate cancer patients with high SOX2 mRNA expression have gene enrichment in cell cycle and DNA damage repair pathways. One protein that regulates cell cycle progression and transcribes DNA damage repair proteins is E2F1. This thesis found that E2F family gene targets are upregulated in response to increased SOX2 expression and that SOX2 targets the E2F1 promoter. Currently, there are few biomarkers for treatment outcomes in prostate cancer. To address this gap, I aim to better understand SOX2 in prostate cancer disease to build a foundation for SOX2 as a predictive marker in patient care.