Apoptosis promotes early tumorigenesis.
1Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA. tangd2@upmc.edu
Oncogene
|December 15, 2010
Summary
Cancer cells often resist apoptosis, a programmed cell death process. However, surprisingly, key apoptosis inducers like CD95 and PUMA can paradoxically promote tumor growth, revealing complex roles in cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Cancer is characterized by resistance to apoptosis.
- Apoptosis plays a critical role in preventing uncontrolled cell proliferation.
- The dual role of apoptosis in cancer is an area of active investigation.
Purpose of the Study:
- To investigate the seemingly paradoxical roles of apoptosis regulators in tumorigenesis.
- To explore how CD95/Fas/Apo1 and PUMA contribute to cancer promotion.
- To understand the complex involvement of apoptosis in the multifaceted nature of cancer development.
Main Methods:
- Review of recent studies on apoptosis regulators in cancer.
- Analysis of the roles of CD95/Fas/Apo1 in death receptor pathway activation.
- Examination of p53 upregulated mediator of apoptosis/PUMA in mitochondrial apoptotic pathway induction.
Main Results:
- CD95/Fas/Apo1, a death receptor pathway inducer, was found to promote tumorigenesis.
- p53 upregulated mediator of apoptosis/PUMA, a mitochondrial pathway inducer, also demonstrated pro-tumorigenic effects.
- These findings challenge conventional understanding of apoptosis's role in cancer.
Conclusions:
- Apoptosis regulators CD95/Fas/Apo1 and PUMA have complex, context-dependent roles in cancer.
- These proteins can paradoxically promote tumorigenesis, highlighting intricate mechanisms in cancer biology.
- Further research is needed to fully elucidate the multifaceted roles of apoptosis in cancer development and progression.
Related Concept Videos
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...