Cancer Biol 2008 Dennis notes

Cancer Biol 2008 Dennis notes -...

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What is autophagy? ouroboros The delivery of cytoplasmic contents to the lysosome (metazoans) or vacuole (yeast) where they are degraded. - turns over proteins, protein complexes and organelles to maintain cytoplasmic homeostasis - provides anabolic precursors necessary for cell survival during nutrient deprivation - may participate in cell death decisions (either pro or anti)
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Mizushima et al. MBC 15, 1101 (2004)
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Is autophagy good or bad for a cancer cell?
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Anticancer therapeutics, autophagy and cell death
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Breast cancer cells -tamoxifen +tamoxifen Bax/Bak -/- MEFs -etoposide +etoposide Leukemia cells -arsenic trioxide +arsenic trioxide Increased vacuolarization in cancer cells treated with chemotherapeutics
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Normal Autophagic (type II) Apoptotic (type I) Necrotic (type III) Cell morphology related to different forms of cell death
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Characterization of Type II Autophagic Cell Death
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Unformatted text preview: Characteristics-accumulation of autophagic vacuoles- mitochondrial dilation- enlargement of the endoplasmic reticulum and golgi apparatus- degradation of cytoplasmic components preceeding nuclear collapse Outstanding question Does the affected cell actually die by autophagy or is vacuolarization a result of a separate death mechanism? Alternate possibilities-death signal may come from a dysfunctional lysosome causing vacuolar accumulation-autophagy may act cytostatically and death signal may be distinct (perhaps apoptotic)-autophagy is acting as a prosurvival pathway that antagonizes the death signal but is eventually overcome Liang et al. Nature 402, 672 (1999) Liang et al. Nature 402, 672 (1999) Qu et al. J Clin Invest 112, 1809 (2003) Yue et al. PNAS 100, 15077 (2003)...
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