Abstract P131: The role of UDP-6 glucose dehydrogenase (UGDH) in estrogen-mediated phenotypes in both estrogen receptor positive and estrogen receptor negative breast cancer

A better understanding of pathologic mechanisms underlying breast cancer progression and metastasis is critical to improve current treatment modalities. UDP-6- glucose dehydrogenase (UGDH) is an enzyme that has become a recent oncologic target of interest across various cancer subtypes for its role in increasing the aggressiveness and migratory capacity of tumor cells both in vitro and in vivo. UGDH is ubiquitously expressed and plays a critical role in forming the extracellular matrix (ECM), producing nucleotide sugars, and processing hormones through glucuronidation. For these reasons, investigating the effect of UGDH on breast cancer in the setting of hormonal stimulation is important. We found that knocking down UGDH in estrogen receptor positive (ER+) breast cancer cell lines (MCF7 marco and T47D) and an estrogen receptor negative (ER-) breast cancer cell line (MDA-MB-231) could abrogate estrogen induced migration-specific phenotypes in vitro. Furthermore, we found that knocking down UGDH mitigated estrogen stimulated primary tumor growth in vivo for both MCF7 macro and MDA-MB-231 mammary fat pad tumor models in mice. Thus, we found that UGDH regulates estrogen stimulated migratory phenotypes in both ER+ and ER- breast cancers in vitro and primary tumor growth in vivo. For this reason, UGDH and its associated pathways are promising targets for future drug development and small molecular targets in the treatment of both metastatic ER positive and ER negative breast cancers. Citation Format: Meghan Price, Catherine Lavau, Cesar Baeta, Jovita Byemerwa, Suzanne Wardell, Olivia Brueckner, Debarati Mukherjee, Corinne Haynes, Annee Nguyen, Chingyi Chang, Donald McDonnell, C. Rory Goodwin. The role of UDP-6 glucose dehydrogenase (UGDH) in estrogen-mediated phenotypes in both estrogen receptor positive and estrogen receptor negative breast cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P131.