Introduction to Cancer Biology (Part 2): Loss of Apoptosis
Summary
TLDRApoptosis, or programmed cell death, is essential for controlling cell growth and maintaining tissue homeostasis. Its absence can lead to uncontrolled cell proliferation, a key factor in cancer development. The script discusses the two main pathways of apoptosis activation: the extrinsic, triggered by tumor necrosis factor receptors, and the intrinsic, initiated by DNA damage. Both pathways involve caspases, which interact with inhibitors and proteins like the bcl2 family. Resistance to apoptosis in malignant cells can occur through overexpression of anti-apoptotic proteins, such as survivin and bcl2. Anti-cancer agents targeting these molecules and the ubiquitin-proteome pathway, which regulates cell cycle proteins, are highlighted as promising treatments for cancer.
Takeaways
- 🛡️ Apoptosis is a crucial mechanism for controlling cell growth and maintaining tissue homeostasis.
- 🚫 The absence of apoptosis can lead to uncontrolled cell growth, a key factor in the development of cancer.
- 🔄 Genetic alterations in cancer cells often result in increased cell proliferation and a loss of apoptosis.
- 🧬 Apoptosis is characterized by cell shrinkage, DNA fragmentation, and the formation of apoptotic bodies.
- 🔬 Phagocytosis is the process by which cells clear apoptotic bodies through the engulfment and recycling of cellular debris.
- 🔄 There are two pathways that activate apoptosis: the death receptor (extrinsic) pathway and the mitochondrial (intrinsic) pathway.
- 🚀 Caspases are enzymes that play a central role in both apoptosis pathways by interacting with various regulatory proteins.
- 🛡️ Resistance to apoptosis in malignant cells can be due to overexpression of anti-apoptotic proteins like survivin and bcl2.
- 🧬 Anti-sense oligonucleotides have been designed to target and reduce the translation of anti-apoptotic proteins.
- 🔄 Overexpression of transcription factors like NF-kB can lead to increased transcription of anti-apoptotic proteins, contributing to apoptotic resistance.
- 💊 Proteasome inhibitors, such as bortezomib (Velcade), have shown promise in treating multiple myeloma by inhibiting the proteasome and reducing anti-apoptotic proteins.
Q & A
What is apoptosis and why is it important for an organism?
-Apoptosis, or programmed cell death, is a mechanism that organisms use to limit the growth and replication of cells. It is crucial for controlling cell growth, maintaining tissue homeostasis, and preventing diseases like cancer.
What would happen if apoptosis did not occur in an organism?
-If apoptosis did not occur, there would be no way to control cell growth, leading to a loss of tissue homeostasis and potentially causing diseases such as cancer due to uncontrolled cell proliferation.
How does apoptosis play a role in cancer?
-In cancer, genetic alterations in cells lead to increased cellular proliferation and growth, as well as a loss of apoptosis. This results in too much cell growth and too little cell death in malignant tissues.
What is the average number of cells that undergo apoptosis in a human adult daily?
-In an average human adult, 50 to 70 billion cells undergo apoptosis per day.
What are the characteristics of apoptosis in normal cells?
-Apoptosis in normal cells is characterized by cell shrinkage, mitochondrial cytochrome C release, fragmentation of cell DNA into multiples of 180 base pairs, and the ultimate breakage of cells into small apoptotic bodies that are cleared through phagocytosis.
What is phagocytosis and how does it relate to apoptosis?
-Phagocytosis is a process where cells take in cell fragments or microorganisms in membrane-bound vesicles. The vesicles fuse with lysosomes containing proteases, and the engulfed material is processed for recycling. This process is essential for clearing apoptotic bodies.
What are the two pathways that can activate apoptosis?
-The two pathways that can activate apoptosis are the death receptor or extrinsic pathway, triggered by activation of members of the tumor necrosis factor receptor superfamily, and the mitochondrial or intrinsic pathway, initiated by DNA damage.
What are caspases and what role do they play in apoptosis?
-Caspases are a set of enzymes that are stimulated by both the extrinsic and intrinsic pathways of apoptosis. They interact with Inhibitors of Apoptosis proteins (IAPs) and the Bcl2 family of proteins, which have either pro- or anti-apoptotic properties.
Why do some malignant cells show resistance to apoptosis?
-Some malignant cells show resistance to apoptosis due to the overexpression of anti-apoptotic proteins, such as survivin, an IAP found in many cancers, and Bcl2, which is overexpressed in B cell lymphomas due to gene translocation.
How have anti-cancer agents been developed to target anti-apoptotic molecules?
-Anti-cancer agents have been developed by designing short segments of DNA complementary to the RNA of anti-apoptotic proteins like Bcl2, known as anti-sense oligonucleotides, to reduce the translation of these proteins and inhibit their anti-apoptotic effects.
What is the role of the ubiquitin-proteome pathway in regulating apoptosis?
-The ubiquitin-proteome pathway regulates the expression of transcription factors and other cell cycle proteins. Certain molecules can suppress or reduce NF-kB and AP1 activation, inhibiting tumor promotion. An example is bortezomib (Velcade), a proteasome inhibitor that has shown promising results in multiple myeloma by inhibiting the proteasome, leading to increased levels of the NF-kB inhibitor and therefore less anti-apoptotic proteins.
Outlines
💀 Understanding Apoptosis and Its Role in Cancer
Apoptosis, or programmed cell death, is essential for controlling cell growth and maintaining tissue homeostasis. Its absence can lead to uncontrolled cell proliferation, a hallmark of cancer. Genetic alterations in cancer cells can result in both increased cell growth and a loss of apoptosis. In normal cells, apoptosis removes damaged cells and maintains a constant cell number in regenerating tissues, playing a crucial role in embryogenesis. On average, 50 to 70 billion cells in a human adult undergo apoptosis daily. The process is characterized by cell shrinkage, mitochondrial cytochrome C release, DNA fragmentation, and the formation of apoptotic bodies that are cleared through phagocytosis. There are two pathways that can activate apoptosis: the death receptor or extrinsic pathway, triggered by the tumor necrosis factor receptor superfamily, and the mitochondrial or intrinsic pathway, initiated by DNA damage. Both pathways activate caspases, enzymes that interact with inhibitors of apoptosis proteins (IAPs) and the bcl2 family of proteins, which have pro- and anti-apoptotic properties. Resistance to apoptosis in malignant cells can be due to the overexpression of anti-apoptotic proteins like survivin and bcl2, which are associated with poor outcomes in various cancers.
Mindmap
Keywords
💡Apoptosis
💡Cellular Proliferation
💡Tissue Homeostasis
💡Cancer
💡Mitochondrial Cytochrome C Release
💡Phagocytosis
💡Death Receptor Pathway
💡Mitochondrial Pathway
💡Caspases
💡Inhibitors of Apoptosis Proteins (IAP)
💡Bcl2 Family
💡Anti-Cancer Agents
💡Nuclear Factor Kappa B (NF-κB)
💡Proteasome Inhibitors
Highlights
Apoptosis is a critical mechanism for controlling cell growth and maintaining tissue homeostasis.
The absence of apoptosis can lead to uncontrolled cell growth and potentially cancer.
Genetic alterations in cancer cells often result in increased proliferation and loss of apoptosis.
Apoptosis in normal cells is essential for the removal of damaged cells and maintaining cell numbers in regenerating tissues.
Embryogenesis is an important process where apoptosis plays a key role.
On average, 50 to 70 billion cells in a human adult undergo apoptosis daily.
Characteristics of apoptosis include cell shrinkage, mitochondrial cytochrome C release, and DNA fragmentation.
Apoptotic bodies are cleared through phagocytosis, a process involving the fusion of vesicles with lysosomes.
There are two pathways that can activate apoptosis: the death receptor (extrinsic) and mitochondrial (intrinsic) pathways.
Caspases are enzymes stimulated by both apoptosis pathways and interact with IAP and Bcl2 family proteins.
Resistance to apoptosis in some malignant cells can be due to overexpression of anti-apoptotic proteins like survivin and Bcl2.
Anti-cancer agents targeting anti-apoptotic molecules, such as bcl2 antisense oligonucleotides, have been developed.
Activation of transcription factors like NF-kB can lead to apoptotic resistance by increasing transcription of anti-apoptotic proteins.
The ubiquitin-proteome pathway regulates the expression of transcription factors and cell cycle proteins.
Bortezomib (Velcade) is a proteasome inhibitor that has shown promising results in multiple myeloma by reducing anti-apoptotic proteins.
Certain molecules can suppress NF-kB and AP1 activation, potentially inhibiting tumor promotion.
Transcripts
apoptosis or programmed cell death is
one of the mechanisms by which organisms
limit the growth and replication of
cells if apoptosis did not occur there
would be no way to control cell growth
and tissue homeostasis would be lost in
fact this is one of the key mechanisms
behind cancer the genetic alterations in
the cancer cell not only lead to
increase cellular proliferation and
growth they also lead to loss of
apoptosis along with too much cell
growth there is too little cell death in
malignant
tissue apoptosis occurs in normal cells
to allow for removal of damage cells
maintain a constant number of cells in
regenerating tissues and is an important
part of
embryogenesis in an average human adult
50 to 70 billion cells undergo apoptosis
per day today apoptosis is characterized
by changes such as cell shrinkage
mitochondrial cytochrome C release
fragmentation of cell DNA into multiples
of 180 base pairs and the ultimate
breakage of cells into small apoptotic
bodies which will be cleared through
phagocytosis phagocytosis is a process
where cells take in cell fragments or
microorganisms in membranebound vesicles
the vesicles fuse with lome containing
proteases and the engulfed material is
processed for recycling there are two
Pathways that can activate
apoptosis the first is the death
receptor or extrinsic pathway it is
triggered by activation of members of
the tumor necrosis factor receptor super
family the second means of initiating
apoptosis is through the mitochondrial
or intrinsic pathway this is set in
motion by DNA
damage both Pathways ultimately
stimulate a set of enzymes called
caspases the caspases interact with
Inhibitors of apoptosis proteins or IAP
and the bcl2 family of proteins which
individually have either Pro and
anti-apoptotic
properties in some maligant cells there
is resistance to apoptosis due to
overexpression of anti-apoptotic protein
prots for example survivin is an IAP
that is found in many Cancers and
predicts for poor outcomes and bcl2 is
overexpressed in B cell lymphomas as a
result of the translocation of its gene
conversely deactivating mutations of a
proapoptotic molecule like back is seen
in some gastrointestinal tumors and
leukemias anti-cancer agents have been
developed targeting anti-apoptotic
molecules for instance short segments of
DNA complementary to the RNA of bcl2 or
anti-sense
oligonucleotides have been designed to
reduce the translation of this
anti-apoptosis
protein activation of transcription
factors can lead to apoptotic resistance
this occurs for example when members of
the nuclear Factor Kappa b or NF Capa
family of transcription factors are
overexpressed in certain tumors which
lead to increase transcription of
anti-apoptotic members of the IAP and
bcl2
families the ubiquit and protome pathway
regulates the expression of
transcription factors and other cell
cycle proteins certain molecules can
suppress or reduce NF Capa B and AP1
activation and inhibit tumor promotion
bordom or velcade is a protome inhibitor
that has shown promising results in
multiple Myoma it inhibits the protome
which leads to increased levels of the
nfca B inhibitor and therefore less
antiapoptotic
proteins
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