A molecular signature for anastasis, recovery from the brink of apoptotic cell death

• Published in: The Journal of cell biology Vol. 216; no. 10; pp. 3355 - 3368
• Main Authors: Sun, Gongping, Guzman, Elmer, Balasanyan, Varuzhan, Conner, Christopher M, Wong, Kirsten, Zhou, Hongjun Robin, Kosik, Kenneth S, Montell, Denise J
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.10.2017; The Rockefeller University Press
• Subjects: Apoptosis; Apoptosis - genetics; Caspase; Cell death; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Cells; Gene expression; Gene sequencing; HeLa Cells; Humans; Proteases; Recovery; Ribonucleic acid; RNA; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Wound healing; Wound Healing - genetics
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201706134

During apoptosis, executioner caspase activity has been considered a point of no return. However, recent studies show that cells can survive caspase activation following transient apoptotic stimuli, a process called anastasis. To identify a molecular signature, we performed whole-transcriptome RNA sequencing of untreated, apoptotic, and recovering HeLa cells. We found that anastasis is an active, two-stage program. During the early stage, cells transition from growth-arrested to growing. In the late stage, HeLa cells change from proliferating to migratory. Recovering cells also exhibited prolonged elevation of proangiogenic factors. Strikingly, some early-recovery mRNAs, including Snail, were elevated first during apoptosis, implying that dying cells poise to recover, even while under apoptotic stress. Snail was also required for recovery. This study reveals similarities in the anastasis genes, pathways, and cell behaviors to those activated in wound healing and identifies a repertoire of potential targets for therapeutic manipulation.