Lorea Valcarcel-Jimenez, Connor Rogerson, Cissy Yong, Christina Schmidt, Ming Yang, Monica Cremades-Rodelgo, Victoria Harle, Victoria Offord, Kim Wong, Ariane Mora, Alyson Speed, Veronica Caraffini, Maxine Gia Binh Tran, Eamonn R Maher, Grant D Stewart, Sakari Vanharanta, David J Adams, Christian Frezza
Fumarate hydratase (FH) is a mitochondrial enzyme that catalyzes the reversible hydration of fumarate to malate in the tricarboxylic acid (TCA) cycle. Germline mutations of FH lead to hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a cancer syndrome characterized by a highly aggressive form of renal cancer. Although HLRCC tumors metastasize rapidly, FH-deficient mice develop premalignant cysts in the kidneys, rather than carcinomas. How Fh1 -deficient cells overcome these tumor-suppressive events during transformation is unknown...
October 21, 2022: Science Advances