Abstract PS19-25: Metastatic TNBC is highly associated with a fused mitochondrial morphology and a glycolytic and lipogenic metabolism programmation

Abstract

Abstract Background: Triple negative breast cancer (TNBC) is characterized by heterogeneous metastatic and metabolic properties, which difficult the diagnosis and development of specific treatment. Therefore, the understanding of the mitochondria´s role in the different grades of TNBC could be relevant for the design of novel specific TNBC treatments. This research aimed to explore the mitochondria morphology and gene expression of proteins related to oxidative and non-oxidative metabolism in metastatic and non-metastatic TNBC cell lines. Methods: We performed a gene expression analysis of mitochondrial biogenesis, EMT and principal metabolism-related genes (Integrated DNA Technologies, CA, USA) in three breast cancer cell lines HCC-1395, MDA-MB-231 and MCF-12A. After the gene expression qPCR data mining, in sílico analisis were performed using confocal microscopy (Leica Microsystems,WZL, DE) in the cell lines where mitochondrial distribution, morphology, function and ROS production were measured. Results: The metastatic TNBC-cell line showed a preference for fatty acid biosynthesis and glycolytic metabolism since overexpression of genes related to both pathways was observed. These metabolism features were accompanied by a fused mitochondrial morphology and lower mitochondrial activity since was observed less mitochondrial density accompanied by the downregulated expression of biogenesis-related genes such as PGC1α. In contrast, the non-metastatic TNBC-cell line presented a hyperfragmented mitochondria, a stress associated mitochondrial morphology accompanied by upregulated expression of mitochondrial biogenesis-related genes, both characteristics related to the higher ROS production observed in this cell line. Conclusions: Metastatic TNBC was characterized by a mitochondrial function and morphology similar to control ranges with a metabolic gene program directed to glycolysis and FA usage. While mitochondria of the non-metastatic TNBC cell line was characterized by a higher density and potential, related to an increase of mitochondrial biogenesis, which in turn was associated with higher levels of ROS and with the consequence of a hyperfragmented mitochondrial morphology. These characteristics can provide a better understanding of the metastasis observed in TNBC and contribute to the development of a specific and personalized TNBC therapy. Key words: Triple Negative Breast Cancer, Mitochondria, Cell-metabolism. Citation Format: Claudia D Aguayo-Millán, Perla Perez-Trevino, Sandra Santuario-Facio, Alberto Camacho, Noemí Garcia, Rocio Ortiz-Lopez. Metastatic TNBC is highly associated with a fused mitochondrial morphology and a glycolytic and lipogenic metabolism programmation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-25.