Department of Medical Biology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
Department of Multidisciplinary Molecular Medicine, Institute of Graduate Studies, Ondokuz Mayis University, Samsun, Turkey.
Mol Diagn Ther. 2024 Jul;28(4):403-423. doi: 10.1007/s40291-024-00718-w. Epub 2024 Jun 18.
Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts.
细胞凋亡，或程序性细胞死亡，通过清除受损或不必要的细胞来维持组织内稳态。然而，细胞可以逃避这个过程，导致癌症等疾病的发生。逃避机制包括失巢凋亡、线粒体 DNA 耗竭、细胞 FLICE 抑制蛋白 (c-FLIP)、内体分选复合物必需运输 (ESCRT)、有丝分裂滑溜、复活和 blebbishield 形成。失巢凋亡是由细胞从细胞外基质中脱离触发的，在癌症研究中至关重要，因为它在细胞存活和转移中发挥作用。线粒体 DNA 耗竭与细胞功能障碍和乳腺癌、前列腺癌等疾病有关，与细胞凋亡抵抗有关。c-FLIP 蛋白家族，特别是 CFLAR，作为一种截断的 caspase-8 形式调节细胞死亡过程。ESCRT 复合物通过增加 Ca2+水平来修复细胞内损伤，从而帮助逃避细胞凋亡。抗有丝分裂剂在癌症治疗中诱导有丝分裂阻滞，但会导致有丝分裂滑溜和四倍体细胞形成。复活使细胞能够抵抗各种触发因素诱导的细胞凋亡。blebbishield 形成通过将凋亡细胞转化为 blebbishields 来间接抑制癌症干细胞中的细胞凋亡。总之，细胞凋亡研究的未来为创新治疗方法、增强诊断工具以及更深入地了解控制细胞命运的复杂生物学过程提供了令人兴奋的可能性。分子生物学、遗传学、免疫学和生物信息学等跨学科的合作将是实现这些前景并改善不同疾病背景下患者结局的关键。
