Abstract 781: Impact of vitamin D and pyruvate carboxylase on hypoxia inducible lipid droplet associated (HILPDA) protein in metastatic breast cancer cells

Abstract

Abstract Metastatic breast cancer, a critical health issue for women globally, is closely linked to aberrant lipid metabolism. One feature of this dysregulated metabolism is the increase in lipid storage in the form of cytoplasmic lipid droplets (CLDs), although what drives their accumulation or their role in metastasis is not clear. In prior studies, we demonstrated that the active form of vitamin D (1,25-dihydroxyvitamin D, 1,25(OH)2D) downregulates pyruvate carboxylase (PC), a key metabolic enzyme, thereby reducing lipid accumulation in metastatic breast cancer cells (MCF10CA1a). Additionally, we have demonstrated that both 1,25(OH)2D treatment and PC-inhibition reduce breast cancer cell migration. Therefore, the goal of the current research is to identify the proteins associated with CLDs in metastatic MCF10CA1a breast cancer cells following 1,25(OH)2D treatment or reduction in PC expression (shPC). Proteins from CLDs and whole cell lysates (WCL) were processed for untargeted proteomic analysis. In the CLD fractions, 1562 identified enriched proteins were common to both MCF10CA1a and 1,25(OH)2D treated cells, while 160 proteins were higher in the MCF10CA1a cells, and 550 proteins were higher in the 1,25(OH)2D-treated cells compared to MCF10CA1a CLD fraction. In the CLD fractions, MCF10CA1a and shPC cells had a similar level of 380 enriched proteins, although 65 were higher in the shPC compared with MCF10CA1a, whereas 1268 were more enriched in the MCF10CA1a CLD fraction. Hypoxia Inducible Lipid Droplet Associated (HILPDA, known to inhibit triacylglycerol lipolysis) was only enriched in the CLD fraction of the metastatic MCF10CA1a cells. HILPDA was not identified in the CLDs of the 1,25(OH)2D treated or the shPC cells, nor in any WCL fraction. Further investigation of HILPDA is important to determine if HILPDA plays a role in dysregulated cellular metabolism, including CLD accumulation, or migration, and may potentially be a target for future therapies to prevent breast cancer progression. Citation Format: Yazhen Song, Chaylen Andolino, Dorothy Teegarden. Impact of vitamin D and pyruvate carboxylase on hypoxia inducible lipid droplet associated (HILPDA) protein in metastatic breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 781.