线粒体在肝细胞癌干细胞维持中的作用
Mitochondria's Role in the Maintenance of Cancer Stem Cells in Hepatocellular Carcinoma
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影响因子:4.2
分区:医学3区 / 细胞与组织工程3区 细胞生物学3区 医学：研究与实验3区
发表日期:2025 Jan
作者:
Manar A Elhinnawi, Michael Ibrahim Boushra, Donia Mohamed Hussien, Fatema Hesham Hussein, Islam Ahmed Abdelmawgood
DOI:
10.1007/s12015-024-10797-1
摘要
肝细胞癌（HCC）是肝癌的主要类型，被认为是全球癌症相关死亡的主要贡献者之一。癌症干细胞（CSCs）是一小群具有显著自我再生能力、肿瘤形成能力和分化潜能的癌细胞。CSCs在癌症的发生、扩散、复发以及对治疗的抵抗中起着关键作用，因此，它们成为治疗干预的潜在目标。通过有效靶向能清除癌症干细胞的药物，有望实现HCC的治愈。线粒体在赋予癌症干细胞药物抗性方面起着核心作用，主要通过线粒体代谢、生物发生和动力学调控。线粒体的氧化磷酸化（OXPHOS）、钙信号和活性氧（ROS）生成的功能障碍，均与人类恶性肿瘤的发生和进展相关，包括HCC。ROS的作用具有双重性，既有益也有害，取决于其浓度。因此，ROS已成为HCC基础机制研究中的重要内容。此外，癌症干细胞的一个特征是线粒体生物发生过程的失衡，线粒体生物合成的增加与其抵抗能力增强密切相关。本文详细探讨了线粒体在维持癌症干细胞及HCC扩散中的作用。深入理解线粒体在肿瘤发生及药物抗性中的作用，有望促进新型抗癌治疗策略的开发。
Abstract
Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is recognized as a major contributor to cancer-related mortality worldwide. Cancer stem cells (CSCs) are a tiny group of cancer cells that possess a significant ability to regenerate themselves, form tumors, and undergo differentiation. CSCs have a pivotal role in the initiation, spread, recurrence, and resistance to treatment of cancer. As a result, they are very susceptible to being targeted for therapeutic intervention. The potential to cure HCC may be achieved by efficiently targeting drugs that eradicate cancer stem cells. Mitochondria have a crucial function in granting drug resistance to cancer stem cells by means of mitochondrial metabolism, biogenesis, and dynamics. Dysfunction in mitochondrial metabolic processes, such as mitochondrial oxidative phosphorylation (OXPHOS), calcium signaling, and reactive oxygen species (ROS) generation, contributes to the initiation and progression of human malignancies, including HCC. ROS have both beneficial and detrimental effects depending on their concentration. Consequently, ROS have become a prominent subject in the study of the fundamental mechanisms of HCC. Furthermore, an imbalance in the process of creating new mitochondria is a characteristic feature of CSCs, and an increase in mitochondrial biogenesis is associated with the heightened resistance observed in CSCs. This article provides a detailed examination of the involvement of mitochondria in the preservation of CSCs, as well as the spread of HCC. A deeper understanding of how mitochondria participate in tumorigenesis and drug resistance could result in the discovery of novel cancer treatments.