Selenium-Binding Protein 1 in Prostate Cancer
thesisposted on 2020-05-01, 00:00 authored by Mostafa Elhodaky
In prostate cancer and several other types of cancer, selenium-binding protein 1 (SBP1) levels are reduced compared to benign tissues, therefore indicating a possible tumor suppressor function for this protein. Here we demonstrate evidence that ectopic expression of SBP1 alters the metabolism of prostate cancer cells by inhibiting oxidative phosphorylation and activating AMPK, a central cellular energy sensor. Additionally, both products of SBP1, H2O2, and H2S, can activate AMPK. SBP1 also inhibits prostate cancer cell migration and growth in semi-solid media. Mutating the SBP1 likely selenium binding site at cys57 does not affect the SBP1-induced AMPK activation, suppression of migration, or growth in semi-solid media. We also identified hepatic nuclear factor 4α (HNF4α) as a novel suppressor of SBP1 expression in prostate cancer cells. In summary, the loss of SBP1 may be a key player during the process of metabolic transformation in prostate cancer and may facilitate the shift towards a malignant phenotype.