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What is anoikis?
Apoptotic cell death caused when ECM-bound cells detach.
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How is anoikis activated?
By integrin receptors.
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Is anoikis intrinsic or extrinsic?
Mostly intrinsic.
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Why does anoikis occur?
To remove cells that may threaten structure of multicellular organisms.
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The ___ family of proteins can be both ___ and ___.
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Give examples of pro-apoptotic proteins.
- Bax, Bak, Mtd
- BH3-only (e.g. Bid, etc)
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Give examples of anti-apoptotic proteins.
Bcl-2, Mcl-1
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Pro-apoptotic proteins are usually synthesized in ___ form and are ___ by ___.
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In normal cells, ___ is found in the cytosol and ___ is found in the mitochondria.
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What might result in the upregulation of BH3-only proteins?
DNA damage, starvation, or cell detachment
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When ___ and ___ dimerize in the mitochondrial membrane, ___ is released.
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___ binding to the ECM and ___ activate pro-survival signals.
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Name three growth factors that activate pro-survival signals.
ERK, JNK, AKT
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___ binding between neighboring cells can ___ apoptosis by blocking ___.
- Cadherin
- prevent
- BH3-only proteins
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___ is a transcription factor that is present in ___ and is ___-apoptotic.
- NF-KB
- every cell type
- anti-
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Detachment from the ECM results in: ___.
- Pro-survival proteins are not activated.
- Inhibition of apoptotic pathways is removed.
- Increased expression of Fas receptors on membrane.
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Describe the two classes of cells for the extrinsic pathway.
- Class 1 - cas8 activation is sufficient to activate cas3
- Class 2 - cas8 insuff for cas3. Activates intrinsic pathway - Bid, CytC.
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What are two basic strategies for anoikis resistance?
- Stimulation of survival signals.
- Inhibition of pro-apoptotic signals.
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What types of cells may have anoikis resistance?
- Cells that migrate in early development.
- Cancer cells.
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How do cells acquire anoikis resistance for migration?
- Constitutive active expression of AKT, MEK, ERK, NF-KB, etc.
- Change in integrin expression (e.g. melanoma).
- Expression of ROS in cancer cells.
- Low O2 environ inhibits pro-apop (e.g. cells in middle of tumor).
- Upregulation of Fas inhibitory protein (FLICE).
- Activation of snail, twist, NF-KB (transcription factors for survival).
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How do normal cells inhibit anoikis?
- Maintain ECM attachment.
- Maintain cell-cell contact (e.g. lymph node binding).
- Temp release from ECM for migration.
- Non-adherent cells (e.g. lymphocytes).
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Describe other receptors s.tu. ECM attach -> integrin receptors ->.
- Epidermal growth factor receptor (EGR).
- Platelet-derived GFR.
- Hepatocyte GFR.
- Vascular endothelial GFR.
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How do transiently migratory cells avoid anoikis?
Activation of kinases and the ROS pathway.
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How do lymphocytes avoid anoikis?
Pro-survival signals from cytokines (IL-2, IL-7, IL-15).
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How do cancer cells avoid anoikis?
- Upgregulation of surival signals.
- Inhibition of pro-apoptotic signals.
- Upregulation of GF/Rs (e.g. hijack other cells to release GFs).
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