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Mitochondrial Uncouplers Turn Off Serine Metabolism and Breast Cancer Lung Metastasis | Newswise - Newswise

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Newswise — Mitochondrial serine catabolic pathway (MSCP), also called serine, glycine, and one-carbon metabolism, is essential for cancer cells to produce amino acids, one-carbon units, and reducing equivalents. The pathway is frequently upregulated in tumors: serine hydroxymethyltransferase 2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) are among the most overexpressed metabolic enzymes in human cancers, and their activity supports cancer cell proliferation, redox balance, and metastasis. Cancer cells rely on MSCP when the electron transport chain (ETC) is impaired, yet no effective therapy selectively targets this pathway. Fat mass and obesity-associated protein (FTO), an m⁶A demethylase, can be inhibited by 2-hydroxyglutarate (2-HG). FTO expression is associated with favorable prognosis and is downregulated in breast cancer, yet there is currently no effective way to reactivate FTO in cancer. Given these challenges, there is a need for in-depth research on therapies that safely reactivate respiration and target MSCP in metastatic breast cancer.

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