FBXO7, a tumor suppressor in endometrial carcinoma, suppresses INF2-associated mitochondrial division

Abstract

Abstract Endometrial carcinoma (ECa) is the most common malignant gynecological cancer, with an increased incidence and fatality rate worldwide. Hyperactive INF2-associated mitochondrial division is involved in the occurrence and development of various tumors, including ECa, although the molecular mechanism is unclear. In this study, we confirmed that FBXO7, an E3 ubiquitin ligase, inhibits INF2-associated mitochondrial division through ubiquitination and degradation of INF2 and acts as a tumor suppressor in ECa. Moreover, we found that ECa-associated FBXO7 mutants were defective in the degradation of INF2, promoting ECa cell proliferation and migration through hyperactive INF2-associated mitochondrial division. In addition, our data support the possibility of using the mitochondrial division inhibitor Mdivi-1 in the treatment of FBXO7-mutated ECa. Our study revealed a novel pathogenesis of ECa and may provide a new treatment strategy for ECa patients with FBXO7 mutations.