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Published on: June 7, 2019
Entosis is induced by ultraviolet radiation
Ruoyao Chen1,2, Abhineet Ram3, John G Albeck3
1Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Abstract:
Entosis is a cell death mechanism that is executed through neighbor cell ingestion and killing that occurs in cancer tissues and during development. Here, we identify JNK and p38 stress-activated kinase signaling as an inducer of entosis in cells exposed to ultraviolet (UV) radiation. Cells with high levels of stress signaling are ingested and killed by those with low levels, a result of heterogeneity arising within cell populations over time. In stressed cells, entosis occurs as part of mixed-cell death response with parallel induction of apoptosis and necrosis, and we find that inhibition of one form of cell death leads to increased rates of another. Together, these findings identify stress-activated kinase signaling as a new inducer of entosis and demonstrate cross talk between different forms of cell death that can occur in parallel in response to UV radiation.
Insights
Stress-activated kinase signaling, including JNK and p38, induces entosis, a cell death process. This occurs alongside apoptosis and necrosis, with cell death pathways influencing each other.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Entosis is a programmed cell death mechanism involving cell engulfment, observed in cancer and development.
- The precise triggers and regulation of entosis, particularly in response to environmental stressors, remain incompletely understood.
Purpose of the Study:
- To identify novel inducers of entosis in cells exposed to ultraviolet (UV) radiation.
- To investigate the relationship between entosis and other cell death pathways like apoptosis and necrosis.
Main Methods:
- Exposure of cells to ultraviolet (UV) radiation.
- Analysis of stress-activated kinase signaling pathways (JNK and p38).
- Observation and quantification of entosis, apoptosis, and necrosis rates.
- Pharmacological inhibition of specific cell death pathways.
Main Results:
- JNK and p38 stress-activated kinase signaling were identified as inducers of entosis upon UV exposure.
- Heterogeneity in stress signaling levels within cell populations led to the ingestion and death of highly stressed cells by less stressed neighbors.
- Entosis occurred concurrently with apoptosis and necrosis, forming a mixed-cell death response.
- Inhibition of one cell death pathway (e.g., apoptosis) resulted in increased rates of other pathways (e.g., necrosis or entosis).
Conclusions:
- Stress-activated kinase signaling (JNK/p38) is a newly identified inducer of entosis.
- Entosis is integrated into a broader, parallel cell death response to UV radiation, involving apoptosis and necrosis.
- There is significant cross-talk between distinct cell death mechanisms, where modulating one impacts the others.
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