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Review
. 2024 Jul;28(4):403-423.
doi: 10.1007/s40291-024-00718-w. Epub 2024 Jun 18.

Beyond Death: Unmasking the Intricacies of Apoptosis Escape

Sercan Ergün  1   2 , Senanur Aslan  3 , Dilbeste Demir  4 , Sümeyye Kayaoğlu  4 , Mevsim Saydam  4 , Yeda Keleş  4 , Damla Kolcuoğlu  4 , Neslihan Taşkurt Hekim  4   3 , Sezgin Güneş  4   3
Affiliations
Review

Beyond Death: Unmasking the Intricacies of Apoptosis Escape

Sercan Ergün et al. Mol Diagn Ther. 2024 Jul.

Abstract

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.

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Conflict of interest statement

The authors (S.E., S.A., D.D., S.K., M.S., Y.K., D.K., N.T.H., S.G.) declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Relationship between mtDNA depletion and resistance to apoptosis. This schematic illustrates potential mechanisms underlying the relationship between mitochondrial DNA (mtDNA) depletion and resistance to apoptosis. As depicted, mtDNA depletion may trigger survival error signaling activation, resulting in decreased levels of reactive oxygen species (ROS), retention of pro-apoptotic factors on the membrane, disruption of mitochondrial membrane potential, and an increase in antioxidant regulation. These events collectively promote antiapoptotic pathways, thereby conferring resistance to apoptosis in affected cells
Fig. 2
Fig. 2
Blebbishield formation process.
See this image and copyright information in PMC

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