Nisco Alessia, Tolomeo Maria, Scalise Mariafrancesca, Zanier Katia, Barile Maria
Department of Biosciences, Biotechnologies, and Environment, University of Bari Aldo Moro, Italy.
Department of Biosciences, Biotechnologies, and Environment, University of Bari Aldo Moro, Italy; Department of DiBEST (Biologia, Ecologia e Scienze della Terra), University of Calabria, Arcavacata di Rende, Italy.
Biochim Biophys Acta Rev Cancer. 2024 Sep;1879(5):189149. doi: 10.1016/j.bbcan.2024.189149. Epub 2024 Jul 4.
Flavins and their associated proteins have recently emerged as compelling players in the landscape of cancer biology. Flavins, encompassing flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), serve as coenzymes in a multitude of cellular processes, such as metabolism, apoptosis, and cell proliferation. Their involvement in oxidative phosphorylation, redox homeostasis, and enzymatic reactions has long been recognized. However, recent research has unveiled an extended role for flavins in the context of cancer. In parallel, riboflavin transporters (RFVTs), FAD synthase (FADS), and riboflavin kinase (RFK) have gained prominence in cancer research. These proteins, responsible for riboflavin uptake, FAD biosynthesis, and FMN generation, are integral components of the cellular machinery that governs flavin homeostasis. Dysregulation in the expression/function of these proteins has been associated with various cancers, underscoring their potential as diagnostic markers, therapeutic targets, and key determinants of cancer cell behavior. This review embarks on a comprehensive exploration of the multifaceted role of flavins and of the flavoproteins involved in nucleus-mitochondria crosstalk in cancer. We journey through the influence of flavins on cancer cell energetics, the modulation of RFVTs in malignant transformation, the diagnostic and prognostic significance of FADS, and the implications of RFK in drug resistance and apoptosis. This review also underscores the potential of these molecules and processes as targets for novel diagnostic and therapeutic strategies, offering new avenues for the battle against this relentless disease.
黄素及其相关蛋白最近已成为癌症生物学领域中引人注目的参与者。黄素包括黄素单核苷酸（FMN）和黄素腺嘌呤二核苷酸（FAD），在众多细胞过程中作为辅酶发挥作用，如新陈代谢、细胞凋亡和细胞增殖。它们参与氧化磷酸化、氧化还原稳态和酶促反应早已为人所知。然而，最近的研究揭示了黄素在癌症背景下的扩展作用。与此同时，核黄素转运蛋白（RFVTs）、FAD合酶（FADS）和核黄素激酶（RFK）在癌症研究中也备受关注。这些蛋白质负责核黄素摄取、FAD生物合成和FMN生成，是控制黄素稳态的细胞机制的重要组成部分。这些蛋白质的表达/功能失调与多种癌症相关，突显了它们作为诊断标志物、治疗靶点和癌细胞行为关键决定因素的潜力。本综述全面探讨了黄素以及参与癌症细胞核 - 线粒体相互作用的黄素蛋白的多方面作用。我们深入研究黄素对癌细胞能量代谢的影响、RFVTs在恶性转化中的调节作用、FADS的诊断和预后意义以及RFK在耐药性和细胞凋亡中的影响。本综述还强调了这些分子和过程作为新型诊断和治疗策略靶点的潜力，为对抗这种难治性疾病提供了新途径。
