Oncogene-induced senescence: the bright and dark side of the response
Vassilis G Gorgoulis1, Thanos D Halazonetis
1Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece. vgorg@med.uoa.gr
Abstract:
In late 1990s, it was shown that activated oncogenes are able to induce senescence. Since then large leaps in understanding this phenomenon have been achieved. There is substantial evidence supporting oncogene-induced senescence (OIS) as a potent antitumor barrier in vivo. Multiple pathways participating in cell cycle regulation, DNA damage signaling, immune response, and bioenergetics regulate the process. Despite its beneficial effects the senescent cell is thought to promote carcinogenesis and age-related disease in a nonautonomous manner. Here, we highlight the works dealing with all these aspects and discuss the studies proposing therapeutic exploitation of OIS.
Insights
Oncogene-induced senescence (OIS) acts as a tumor suppressor. However, senescent cells can paradoxically promote cancer and aging, suggesting therapeutic potential for OIS.
Area of Science:
- Oncology
- Cell Biology
- Aging Research
Background:
- Activated oncogenes can trigger cellular senescence, a state with implications for cancer and aging.
- Oncogene-induced senescence (OIS) is recognized as a significant in vivo antitumor mechanism.
- The process involves complex regulation by cell cycle, DNA damage, immune, and bioenergetic pathways.
Purpose of the Study:
- To review the multifaceted roles of OIS in cancer and aging.
- To discuss the dual nature of senescent cells, acting as both a barrier and a promoter.
- To explore therapeutic strategies leveraging OIS.
Main Methods:
- Literature review of studies on OIS.
- Analysis of pathways regulating senescence.
- Examination of OIS's role in carcinogenesis and age-related diseases.
Main Results:
- OIS functions as a potent antitumor barrier.
- Senescent cells exhibit context-dependent roles, potentially promoting disease.
- Multiple cellular pathways are involved in regulating OIS.
Conclusions:
- OIS is a critical defense against cancer, regulated by diverse cellular processes.
- Therapeutic targeting of OIS presents a promising avenue for disease intervention.
- Understanding the dual role of senescent cells is key for future treatments.
Related Concept Videos
02:15Replicative Cell Senescence
02:15Replicative Cell Senescence
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...