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Intercellular induction of apoptosis through modulation of endogenous survival factor concentration: a review
S Dormann1, A Schwieger, J Hanusch
1Abteilung Virologie, Universität Freiburg, Germany.
Abstract:
Fibroblasts constitutively express a functional apoptosis machinery which is under negative control by operationally defined endogenous survival factors. Oncogenic transformation causes a marked downmodulation of endogenous survival factor concentration which renders transformed cells more sensitive to various apoptosis stimuli compared to their nontransformed counterparts. Endogenous survival factors can be inactivated by reactive oxygen species (ROS). Endogenous survival factors are the ultimate targets for apoptosis-inducing factors derived from TGF-beta-triggered nontransformed cells during intercellular induction of apoptosis. During this control step of oncogenesis, endogenous survival factors in transformed cells are inactivated by ROS and the apoptosis machinery is released from negative control. This mechanism leads to the specific elimination of transformed cells. Our data show that the transformed state causes both the ability of the cells to perceive the apoptosis-inducing signal and a decrease in the concentration of endogenous survival factors. These two mechanisms are of central importance for the regulation of intercellular induction of apoptosis.
Insights
Oncogenic transformation sensitizes cells to apoptosis by reducing survival factors, which are inactivated by reactive oxygen species (ROS). This mechanism specifically eliminates transformed cells during oncogenesis.
Area of Science:
- Cell Biology
- Cancer Research
- Apoptosis Signaling
Background:
- Fibroblasts possess an intrinsic apoptosis system regulated by endogenous survival factors.
- Oncogenic transformation downregulates these survival factors, increasing cell sensitivity to apoptosis.
- Reactive oxygen species (ROS) can inactivate endogenous survival factors.
Purpose of the Study:
- To investigate the role of endogenous survival factors and ROS in regulating apoptosis during oncogenesis.
- To elucidate the mechanisms by which transformed cells are eliminated through intercellular apoptosis induction.
Main Methods:
- Analysis of apoptosis machinery in fibroblasts.
- Assessment of endogenous survival factor concentration in transformed vs. nontransformed cells.
- Investigation of ROS involvement in survival factor inactivation and apoptosis induction.
Main Results:
- Oncogenic transformation leads to decreased endogenous survival factor levels, sensitizing cells to apoptosis.
- Reactive oxygen species (ROS) inactivate endogenous survival factors, releasing the apoptosis machinery from negative control.
- Transformed cells exhibit both heightened sensitivity to apoptosis signals and reduced survival factor concentrations.
Conclusions:
- The downregulation of endogenous survival factors and their inactivation by ROS are critical mechanisms for eliminating transformed cells during oncogenesis.
- These processes are central to the regulation of intercellular apoptosis induction and cancer cell elimination.