Background: Fast growing cancer cells require greater amounts of ATP than normal cells. Although glycolysis was suggested as a source of anabolic metabolism based on lactate production, the main source of ATP to support cancer cell metabolism remains unidentified.
Methods: We have proposed that the oxoglutarate carrier SLC25A11 is important for ATP production in cancer by NADH transportation from the cytosol to mitochondria as a malate. We have examined not only changes of ATP and NADH but also changes of metabolites after SLC25A11 knock down in cancer cells.
Findings: The mitochondrial electron transport chain was functionally active in cancer cells. The cytosolic to mitochondrial NADH ratio was higher in non-small cell lung cancer (NSCLC) and melanoma cells than in normal cells. This was consistent with higher levels of the oxoglutarate carrier SLC25A11. Blocking malate transport by knockdown of SLC25A11 significantly impaired ATP production and inhibited the growth of cancer cells, which was not observed in normal cells. In in vivo experiments, heterozygote of SLC25A11 knock out mice suppressed KRAS lung tumor formation by cross breeding.
Interpretation: Cancer cells critically depended on the oxoglutarate carrier SLC25A11 for transporting NADH from cytosol to mitochondria as a malate form for the purpose of ATP production. Therefore blocking SLC25A11 may have an advantage in stopping cancer growth by reducing ATP production. FUND: The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to SYK (NRF-2017R1A2B2003428).
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http://dx.doi.org/10.1016/j.ebiom.2019.01.036 | DOI Listing |
Front Biosci (Landmark Ed)
January 2025
Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy.
Background: Thyroid Hormones (THs) critically impact human cancer. Although endowed with both tumor-promoting and inhibiting effects in different cancer types, excess of THs has been linked to enhanced tumor growth and progression. Breast cancer depends on the interaction between bulk tumor cells and the surrounding microenvironment in which mesenchymal stem cells (MSCs) exert powerful pro-tumorigenic activities.
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January 2025
Division of Biochemistry and Molecular Biology, Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of Russia, 634050 Tomsk, Russia.
Background: Over the past five years, the pregnancy rate in assisted reproductive technology (ART) programs in Russia has remained relatively stable. The aim of this study was to assess the distribution of monocyte and macrophage subsets in the blood and follicular fluid of infertile women undergoing assisted reproductive technology.
Methods: The study involved 45 women with a mean age of 35 ± 4.
Front Biosci (Landmark Ed)
January 2025
Department of Chemoradiotherapy, Ningbo No 2 Hospital, 315000 Ningbo, Zhejiang, China.
Background: Breast cancer stem cells (BCSCs) are instrumental in treatment resistance, recurrence, and metastasis. The development of breast cancer and radiation sensitivity is intimately pertinent to long non-coding RNA (lncRNA). This work is formulated to investigate how the lncRNA affects the stemness and radioresistance of BCSCs.
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January 2025
Department of Oncology, The First Affiliated Hospital of Zhengzhou Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, China.
Endometrial Cancer (EC) is one of the most common gynecological malignancies, ranking first in developed countries and regions. The occurrence and development of EC is closely associated with genetic mutations. mutation, in particular, can lead to the dysfunction of numerous regulatory factors and alteration of the tumor microenvironment (TME).
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January 2025
Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands.
Sulfatides or 3-O-sulfogalactosylceramide are negatively charged sulfated glycosphingolipids abundant in the brain and kidneys and play crucial roles in nerve impulse conduction and urinary pH regulation. Sulfatides are present in the liver, specifically in the biliary tract. Sulfatides are self-lipid antigens presented by cholangiocytes to activate cluster of differentiation 1d (CD1d)-restricted type II natural killer T (NKT) cells.
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