Next, using ovarian cancer xenograft models, the investigators found that inhibiting SCD blocked tumor growth in vivo. Lurie Comprehensive Cancer Center of Northwestern University. So, if there are too many saturated fatty acids, the cell will die, but the unsaturated fatty acids act like a buffer," said Matei, who is also a professor of Medicine in the Division of Hematology and Oncology and a member of the Robert H. "The balance between saturated and unsaturated fatty acids is very important in maintaining the integrity of the endoplasmic reticulum. In contrast, increased levels of unsaturated fatty acids protected cancer cells from cellular stress triggered by the endoplasmic reticulum (ER), a network of tubules in the cytoplasm that transports proteins and lipids throughout the cell. They found that inhibiting or depleting SCD entirely decreased the amount of unsaturated fatty acids in the cancer cells, tipping the balance towards saturated fatty acids. Taking their findings one step further in the current study, the investigators used transcriptomics, lipidomics and single-cell imaging to uncover how SCD regulation of fatty acids impacts the survival of ovarian cancer cells. However, previous work from the Matei laboratory established that cancer stem cells are enriched in unsaturated fatty acids and that targeting SCD eliminated cancer stem cells. While it is known that SCD is essential for maintaining lipid balance in cancer cells, how it influences cancer cell survival and tumor progression has remained poorly understood. This "desaturation" is the final step of lipogenesis, the process of converting metabolites into fatty acids and energy. To maintain proper intracellular functioning, including cellular signaling and lipid storage, saturated fatty acids are converted into unsaturated fatty acids by an enzyme called stearoyl Co-A desaturase (SCD). The study, led by Daniela Matei, MD, the Diana, Princess of Wales Professor of Cancer Research and chief of Reproductive Science in Medicine in the Department of Obstetrics and Gynecology, also suggests that targeting this enzyme in combination with dietary interventions may be a promising treatment strategy for cancer.įatty acids, or lipids, act as an alternative energy source for cancer cells when glucose and oxygen are limited in the tumor microenvironment.
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