2021 journal article
Altered glucuronidation deregulates androgen dependent response profiles and signifies castration resistance in prostate cancer
Oncotarget, 12(19), 1886–1902.
TL;DR:
A role for UGDH in androgen responsiveness and a target for therapeutic strategies in advanced prostate cancer is supported by a comparison of protein and metabolite levels relevant to the glucuronidation pathway in patient-derived xenograft models paired with isogenic counterparts selected in vivo for castration resistant prostate cancer recurrence.
(via Semantic Scholar)
open access via www.oncotarget.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(OpenAlex)
Source: ORCID
Added: July 16, 2022
Glucuronidation controls androgen levels in the prostate and the dysregulation of enzymes in this pathway is associated with castration resistant prostate cancer. UDP-glucose dehydrogenase (UGDH) produces UDP-glucuronate, the essential precursor for glucuronidation, and its expression is elevated in prostate cancer. We compared protein and metabolite levels relevant to the glucuronidation pathway in five prostate cancer patient-derived xenograft models paired with their isogenic counterparts that were selected in vivo for castration resistant (CR) recurrence. All pairs showed changes in UGDH and associated enzymes and metabolites that were consistent with those we found in an isogenic androgen dependent (AD) and CR LNCaP prostate cancer model. Ectopic overexpression of UGDH in LNCaP AD cells blunted androgen-dependent gene expression, increased proteoglycan synthesis, significantly increased cell growth compared to controls, and eliminated dose responsive growth suppression with enzalutamide treatment. In contrast, the knockdown of UGDH diminished proteoglycans, suppressed androgen dependent growth irrespective of androgens, and restored androgen sensitivity in CR cells. Importantly, the knockdown of UGDH in both LNCaP AD and CR cells dramatically sensitized these cells to enzalutamide. These results support a role for UGDH in androgen responsiveness and a target for therapeutic strategies in advanced prostate cancer.