BIO135 Anoikis Notes.txt

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BIO135 Anoikis Notes.txt
2012-05-18 06:24:58
BIO135 Anoikis Notes

BIO135 Anoikis Notes
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  1. What is anoikis?
    Apoptotic cell death caused when ECM-bound cells detach.
  2. How is anoikis activated?
    By integrin receptors.
  3. Is anoikis intrinsic or extrinsic?
    Mostly intrinsic.
  4. Why does anoikis occur?
    To remove cells that may threaten structure of multicellular organisms.
  5. The ___ family of proteins can be both ___ and ___.
    • BCL-2
    • pro-
    • anti-apoptotic
  6. Give examples of pro-apoptotic proteins.
    • Bax, Bak, Mtd
    • BH3-only (e.g. Bid, etc)
  7. Give examples of anti-apoptotic proteins.
    Bcl-2, Mcl-1
  8. Pro-apoptotic proteins are usually synthesized in ___ form and are ___ by ___.
    • inactive
    • activated
    • cutting
  9. Anti-apoptotic proteins are synthesized in what form?
  10. In normal cells, ___ is found in the cytosol and ___ is found in the mitochondria.
    • Bax
    • Bak
  11. What might result in the upregulation of BH3-only proteins?
    DNA damage, starvation, or cell detachment
  12. The upregulation of ___ can result in ___ and ___ to dimerize in the mitochondrial membrane, and thus ___ being released.
    • BH3-only proteins
    • Bak and Bax
    • cytochrome C
  13. ___ binding to the ECM and ___ activate pro-survival signals.
    • Integrin
    • Growth factors
  14. Name three growth factors that activate pro-survival signals.
  15. ___ binding between neighboring cells can ___ apoptosis by blocking ___.
    • Cadherin
    • prevent
    • BH3-only proteins
  16. ___ is a transcription factor that is present in ___ and is ___-apoptotic.
    • NF-KB
    • every cell type
    • anti-
  17. Detachment from the ECM results in: ___.
    • Pro-survival proteins are not activated.
    • Inhibition of apoptotic pathways is removed.
    • Increased expression of Fas (aka death) receptors on membrane.
  18. 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.
  19. What are two basic strategies for anoikis resistance?
    • Stimulation of survival signals.
    • Inhibition of pro-apoptotic signals.
  20. What types of cells may have anoikis resistance?
    • Cells that migrate in early development.
    • Cancer cells.
  21. 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).
  22. 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).
  23. Describe other receptors s.t ECM attach -> integrin receptors -> ligand indep.
    • Epidermal growth factor receptor (EGR).
    • Platelet-derived GFR.
    • Hepatocyte GFR.
    • Vascular endothelial GFR.
  24. How do transiently migratory cells avoid anoikis?
    Activation of kinases and the ROS pathway.
  25. How do lymphocytes avoid anoikis?
    Pro-survival signals from cytokines (IL-2, IL-7, IL-15).
  26. 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).