Autophagy facilitates oncogene-induced senescence
Masako Narita1, Andrew R J Young, Masashi Narita
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK. masashi.narita@cancer.org.uk
Abstract:
Oncogenic stress triggers a range of intracellular protective responses including DNA damage checkpoints, senescence and apoptosis, depending on the cell type and the severity of the particular stress. Senescent cells are metabolically viable but are stably arrested. Senescence is a collective phenotype, however, that is comprised of various signaling pathways and effector mechanisms. Thus, to understand and manipulate the senescence phenotype, it is critical to find its effector mechanisms and determine the relationships between them. We have recently found that autophagy is activated upon acute induction of senescence and facilitates another effector mechanism: the senescence associated secretory phenotype (SASP).
Insights
Oncogenic stress induces protective cellular responses like senescence. Autophagy activation is crucial for senescence, facilitating the senescence-associated secretory phenotype (SASP).
Area of Science:
- Cellular Biology
- Cancer Research
- Molecular Biology
Background:
- Oncogenic stress activates protective cellular responses, including senescence, a stable cell cycle arrest.
- Senescence is a complex phenotype involving multiple signaling pathways and effector mechanisms.
- Understanding these mechanisms is key to manipulating the senescence phenotype.
Purpose of the Study:
- To investigate the role of autophagy in the induction and manifestation of cellular senescence.
- To determine the relationship between autophagy and the senescence-associated secretory phenotype (SASP).
Main Methods:
- Induction of cellular senescence.
- Analysis of autophagy activation.
- Assessment of SASF production.
Main Results:
- Autophagy is activated during acute induction of senescence.
- Autophagy facilitates the development of the senescence-associated secretory phenotype (SASP).
Conclusions:
- Autophagy plays a critical role in the effector mechanisms of cellular senescence.
- Targeting autophagy may provide a means to modulate the SASP and cellular senescence.
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