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Cancers, Vol. 14, Pages 2380: Endocrine Therapy-Resistant Breast Cancer Cells Are More Sensitive to Ceramide Kinase Inhibition and Elevated Ceramide Levels Than Therapy-Sensitive Breast Cancer Cells
In this study, we have investigated how alterations in sphingolipids promote cell survival in ET-resistant breast cancer. We have performed LC-MS-based targeted sphingolipidomics of tamoxifen-sensitive and -resistant MCF-7 breast cancer cell lines. Follow-up studies included treatments of cell lines and patient-derived xenograft organoids (PDxO) with small molecule inhibitors; cytometric analyses to measure cell death, proliferation, and apoptosis; siRNA-mediated knockdown; RT-qPCR and Western blot for gene and protein expression; targeted lipid analysis; and lipid addback experiments. We found that tamoxifen-resistant cel...
Source: Cancers - May 12, 2022 Category: Cancer & Oncology Authors: Purab Pal Alec Millner Svetlana E. Semina Rosemary J. Huggins Logan Running Diana S. Aga Debra A. Tonetti Rachel Schiff Geoffrey L. Greene G. Ekin Atilla-Gokcumen Jonna Frasor Tags: Article Source Type: research

Insulin-like growth factor 1 signaling is essential for mitochondrial biogenesis and mitophagy in cancer cells Metabolism
Mitochondrial activity and metabolic reprogramming influence the phenotype of cancer cells and resistance to targeted therapy. We previously established that an insulin-like growth factor 1 (IGF-1)-inducible mitochondrial UTP carrier (PNC1/SLC25A33) promotes cell growth. This prompted us to investigate whether IGF signaling is essential for mitochondrial maintenance in cancer cells and whether this contributes to therapy resistance. Here we show that IGF-1 stimulates mitochondrial biogenesis in a range of cell lines. In MCF-7 and ZR75.1 breast cancer cells, IGF-1 induces peroxisome proliferator–activated receptor γ coac...
Source: Journal of Biological Chemistry - October 13, 2017 Category: Chemistry Authors: Amy Lyons, Michael Coleman, Sarah Riis, Cedric Favre, Ciara H. O'Flanagan, Alexander V. Zhdanov, Dmitri B. Papkovsky, Stephen D. Hursting, Rosemary O'Connor Tags: Molecular Bases of Disease Source Type: research