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癌症及癌前病变中的线粒体相关通路:机制洞察

Mitochondria-Associated Pathways in Cancer and Precancerous Conditions: Mechanistic Insights.

作者信息

Li Ling, Pan Dan, Ai Ruixue, Zhou Yu

机构信息

State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Department of Clinic Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway.

出版信息

Int J Mol Sci. 2025 Sep 2;26(17):8537. doi: 10.3390/ijms26178537.

Abstract

Mitochondria perform critical roles in cellular functions, particularly in metabolism and cell death regulation. Mutations in nuclear and mitochondrial genes can cause mitochondrial dysfunction, leading to classical mitochondrial diseases. Emerging evidence suggests that mitochondrial adaptations in cancer support the high energy demands of proliferating cells and contribute to tumor progression through anti-apoptotic mechanisms, dysregulated mitochondrial quality control (mtQC), and altered mitochondrial DNA (mtDNA) copy numbers. Interestingly, several mitochondrial pathways involved in cancer progression resemble those implicated in mitochondrial diseases. From this perspective, although cancer is not a classical mitochondrial disease, its progression involves mitochondria-associated pathways similar to those in mitochondrial disorders, suggesting that cancer may be considered a mitochondria-related disease in a broader sense. Understanding these shared mechanisms could provide new insights into precision treatment strategies. Furthermore, mitochondrial dysfunction is increasingly recognized in precancerous conditions, suggesting its potential as a target for early intervention. Oral potentially malignant disorders (OPMDs) serve as a valuable model for studying these mitochondria-associated mechanisms, offering a promising avenue for both therapeutic advancements and preventive approaches.

摘要

线粒体在细胞功能中发挥着关键作用,尤其是在新陈代谢和细胞死亡调控方面。核基因和线粒体基因的突变可导致线粒体功能障碍,引发典型的线粒体疾病。新出现的证据表明,癌症中的线粒体适应性变化支持增殖细胞对高能量的需求,并通过抗凋亡机制、失调的线粒体质量控制(mtQC)以及线粒体DNA(mtDNA)拷贝数的改变促进肿瘤进展。有趣的是,一些参与癌症进展的线粒体途径与线粒体疾病中涉及的途径相似。从这个角度来看,虽然癌症不是典型的线粒体疾病,但其进展涉及与线粒体疾病中相似的线粒体相关途径,这表明癌症在更广泛的意义上可能被视为一种线粒体相关疾病。了解这些共同机制可为精准治疗策略提供新的见解。此外,癌前病变中的线粒体功能障碍越来越受到认可,这表明其作为早期干预靶点的潜力。口腔潜在恶性疾病(OPMDs)是研究这些线粒体相关机制的宝贵模型,为治疗进展和预防方法提供了一条有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4e/12429017/c086d7d49fb5/ijms-26-08537-g001.jpg

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