探索黄素稳态对癌细胞代谢的影响。
Exploring the impact of flavin homeostasis on cancer cell metabolism.
发表日期:2024 Jul 04
作者:
Alessia Nisco, Maria Tolomeo, Mariafrancesca Scalise, Katia Zanier, Maria Barile
来源:
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
摘要:
黄素及其相关蛋白质最近已成为癌症生物学领域引人注目的参与者。黄素,包括黄素单核苷酸 (FMN) 和黄素腺嘌呤二核苷酸 (FAD),在多种细胞过程中充当辅酶,例如代谢、细胞凋亡和细胞增殖。它们参与氧化磷酸化、氧化还原稳态和酶反应早已被认识到。然而,最近的研究揭示了黄素在癌症中的广泛作用。与此同时,核黄素转运蛋白 (RFVT)、FAD 合酶 (FADS) 和核黄素激酶 (RFK) 在癌症研究中得到了重视。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组成部分。这些蛋白质的表达/功能失调与多种癌症有关,强调了它们作为诊断标记物、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和黄素蛋白在癌症中参与核-线粒体串扰的多方面作用。我们探讨了黄素对癌细胞能量学的影响、恶性转化中 RFVT 的调节、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。这篇综述还强调了这些分子和过程作为新型诊断和治疗策略目标的潜力,为对抗这种无情的疾病提供了新途径。版权所有 © 2024。由 Elsevier B.V. 出版。
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.Copyright © 2024. Published by Elsevier B.V.