Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response.

TitleCell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response.
Publication TypeJournal Article
Year of Publication2012
AuthorsTang HLam, Tang HMan, Mak KHou, Hu S, Wang SShan, Wong KMan, Wong CSing Timot, Wu HYan, Law HTung, Liu K, C Talbot C, Lau WKeung, Montell DJ, Fung MChiu
JournalMol Biol Cell
Volume23
Issue12
Pagination2240-52
Date Published2012 Jun
ISSN1939-4586
KeywordsAnimals, Animals, Newborn, Anti-Infective Agents, Local, Antineoplastic Agents, Apoptosis, Cell Survival, Cell Transformation, Neoplastic, Cells, Cultured, Depsipeptides, DNA Damage, Ethanol, Gene Expression Profiling, HeLa Cells, Humans, Liver, Mice, Mice, Inbred BALB C, Microscopy, Fluorescence, Myocytes, Cardiac, NIH 3T3 Cells, Oligonucleotide Array Sequence Analysis, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Transcriptome
Abstract

<p>Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism "anastasis" (Greek for "rising to life"). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity.</p>

DOI10.1091/mbc.E11-11-0926
Alternate JournalMol. Biol. Cell
PubMed ID22535522
PubMed Central IDPMC3374744
Grant ListR01 GM046425 / GM / NIGMS NIH HHS / United States
S10 RR024550 / RR / NCRR NIH HHS / United States
R01GM46425 / GM / NIGMS NIH HHS / United States